Germline-encoded amino acids in the αβ T-cell receptor control thymic selection View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-04

AUTHORS

James P. Scott-Browne, Janice White, John W. Kappler, Laurent Gapin, Philippa Marrack

ABSTRACT

An alphabeta T-cell response depends on the recognition of antigen plus major histocompatibility complex (MHC) proteins by its antigen receptor (TCR). The ability of peripheral alphabeta T cells to recognize MHC is at least partly determined by MHC-dependent thymic selection, by which an immature T cell survives only if its TCR can recognize self MHC. This process may allow MHC-reactive TCRs to be selected from a repertoire with completely random and unbiased specificities. However, analysis of thymocytes before positive selection indicated that TCR proteins might have a predetermined ability to bind MHC. Here we show that specific germline-encoded amino acids in the TCR promote 'generic' MHC recognition and control thymic selection. In mice expressing single, rearranged TCR beta-chains, individual mutation of amino acids in the complementarity-determining region (CDR) 2beta to Ala reduced development of the entire TCR repertoire. Altogether, these results show that thymic selection is controlled by germline-encoded MHC contact points in the alphabeta TCR and indicate that the diversity of the peripheral T-cell repertoire is enhanced by this 'built-in' specificity. More... »

PAGES

1043

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature07812

DOI

http://dx.doi.org/10.1038/nature07812

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017171182

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19262510


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Immunology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Amino Acids", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Bone Marrow", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Chimera", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Complementarity Determining Regions", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Germ Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hybridomas", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Major Histocompatibility Complex", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, Antigen, T-Cell, alpha-beta", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Thymus Gland", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Colorado Denver", 
          "id": "https://www.grid.ac/institutes/grid.241116.1", 
          "name": [
            "Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Scott-Browne", 
        "givenName": "James P.", 
        "id": "sg:person.01360605223.13", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01360605223.13"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Colorado Denver", 
          "id": "https://www.grid.ac/institutes/grid.241116.1", 
          "name": [
            "Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "White", 
        "givenName": "Janice", 
        "id": "sg:person.010157255507.71", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010157255507.71"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Howard Hughes Medical Institute", 
          "id": "https://www.grid.ac/institutes/grid.413575.1", 
          "name": [
            "Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA", 
            "Howard Hughes Medical Institute,", 
            "Department of Medicine,", 
            "Department of Pharmacology,", 
            "Program in Biomolecular Structure and,"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kappler", 
        "givenName": "John W.", 
        "id": "sg:person.01361470371.87", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01361470371.87"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Colorado Denver", 
          "id": "https://www.grid.ac/institutes/grid.241116.1", 
          "name": [
            "Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gapin", 
        "givenName": "Laurent", 
        "id": "sg:person.01064765234.16", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01064765234.16"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Colorado Anschutz Medical Campus", 
          "id": "https://www.grid.ac/institutes/grid.430503.1", 
          "name": [
            "Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA", 
            "Howard Hughes Medical Institute,", 
            "Department of Medicine,", 
            "Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado 80220, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Marrack", 
        "givenName": "Philippa", 
        "id": "sg:person.01066606743.28", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01066606743.28"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1084/jem.177.1.119", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000666423"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4049/jimmunol.164.12.6252", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000967261"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1084/jem.186.7.1149", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003929300"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.immunol.26.021607.090421", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004718812"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1084/jem.147.3.882", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008369492"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1510", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010605813", 
          "https://doi.org/10.1038/ni1510"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/eji.1830010102", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012650964"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2005.05.013", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012919320"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1084/jem.153.5.1198", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014615515"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nri853", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015746364", 
          "https://doi.org/10.1038/nri853"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nri853", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015746364", 
          "https://doi.org/10.1038/nri853"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/336073a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017494831", 
          "https://doi.org/10.1038/336073a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.immunol.23.021704.115658", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019295510"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/248701a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021418039", 
          "https://doi.org/10.1038/248701a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.immuni.2008.01.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026719767"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/335730a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026925225", 
          "https://doi.org/10.1038/335730a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/335730a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026925225", 
          "https://doi.org/10.1038/335730a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.immuni.2004.11.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027550001"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf00172177", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031690752", 
          "https://doi.org/10.1007/bf00172177"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf00172177", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031690752", 
          "https://doi.org/10.1007/bf00172177"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1502", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032706930", 
          "https://doi.org/10.1038/ni1502"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1074-7613(00)80547-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033287487"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/269417a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034526188", 
          "https://doi.org/10.1038/269417a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/269417a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034526188", 
          "https://doi.org/10.1038/269417a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0092-8674(00)81905-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041641914"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0092-8674(86)90591-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041841357"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.iy.13.040195.000521", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045836159"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0092-8674(85)80103-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046706960"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1084/jem.191.8.1355", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047071681"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1084/jem.148.3.766", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048475518"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1074-7613(00)80523-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052289649"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2105-7-225", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052511038", 
          "https://doi.org/10.1186/1471-2105-7-225"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2105-7-225", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052511038", 
          "https://doi.org/10.1186/1471-2105-7-225"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1074-7613(04)00378-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1054680329"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1079346876", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2009-04", 
    "datePublishedReg": "2009-04-01", 
    "description": "An alphabeta T-cell response depends on the recognition of antigen plus major histocompatibility complex (MHC) proteins by its antigen receptor (TCR). The ability of peripheral alphabeta T cells to recognize MHC is at least partly determined by MHC-dependent thymic selection, by which an immature T cell survives only if its TCR can recognize self MHC. This process may allow MHC-reactive TCRs to be selected from a repertoire with completely random and unbiased specificities. However, analysis of thymocytes before positive selection indicated that TCR proteins might have a predetermined ability to bind MHC. Here we show that specific germline-encoded amino acids in the TCR promote 'generic' MHC recognition and control thymic selection. In mice expressing single, rearranged TCR beta-chains, individual mutation of amino acids in the complementarity-determining region (CDR) 2beta to Ala reduced development of the entire TCR repertoire. Altogether, these results show that thymic selection is controlled by germline-encoded MHC contact points in the alphabeta TCR and indicate that the diversity of the peripheral T-cell repertoire is enhanced by this 'built-in' specificity.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/nature07812", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2449844", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2665703", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2681866", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2599494", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2456456", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2434864", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2438855", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2633733", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2665697", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0090-0028", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7241", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "458"
      }
    ], 
    "name": "Germline-encoded amino acids in the \u03b1\u03b2 T-cell receptor control thymic selection", 
    "pagination": "1043", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "51cf6aaef5d1e1dca0b8a9a7eb13a5d06871aa01fd82acd15b23a4af814d337b"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "19262510"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "0410462"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nature07812"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1017171182"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nature07812", 
      "https://app.dimensions.ai/details/publication/pub.1017171182"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T16:28", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8669_00000424.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/nature07812"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature07812'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature07812'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature07812'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature07812'


 

This table displays all metadata directly associated to this object as RDF triples.

274 TRIPLES      21 PREDICATES      71 URIs      33 LITERALS      21 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nature07812 schema:about N3777114487f24961af48361de49185b0
2 N3c61fd5a089e4d4184354bf7def0cb15
3 N4c1e974e6c174dee8ec033d5cb423f49
4 N6bba062ec95045a1960c87e8a63c7299
5 N811283a4e00d4d55beb0cca00dacbce6
6 N8120fc99467e4565ab7a949a10860779
7 N95458fe7133446efbe8e5f8228381dea
8 Nbd422a56e59b4773a2d757c5473f57de
9 Nbdd5fe47f87b4f37ac54cf36bad49baa
10 Nc8c02db41158470ba0e6b224bb45f16e
11 Nfa3e5e8c93534f0a806787608cf7d83d
12 Nfd7b9cd3df9f4eb298a1c331eed74a32
13 anzsrc-for:11
14 anzsrc-for:1107
15 schema:author N163d3c38a41f42a7aec7966e9b790e2f
16 schema:citation sg:pub.10.1007/bf00172177
17 sg:pub.10.1038/248701a0
18 sg:pub.10.1038/269417a0
19 sg:pub.10.1038/335730a0
20 sg:pub.10.1038/336073a0
21 sg:pub.10.1038/ni1502
22 sg:pub.10.1038/ni1510
23 sg:pub.10.1038/nri853
24 sg:pub.10.1186/1471-2105-7-225
25 https://app.dimensions.ai/details/publication/pub.1079346876
26 https://doi.org/10.1002/eji.1830010102
27 https://doi.org/10.1016/0092-8674(86)90591-x
28 https://doi.org/10.1016/j.cell.2005.05.013
29 https://doi.org/10.1016/j.immuni.2004.11.015
30 https://doi.org/10.1016/j.immuni.2008.01.008
31 https://doi.org/10.1016/s0092-8674(00)81905-4
32 https://doi.org/10.1016/s0092-8674(85)80103-3
33 https://doi.org/10.1016/s1074-7613(00)80523-3
34 https://doi.org/10.1016/s1074-7613(00)80547-6
35 https://doi.org/10.1016/s1074-7613(04)00378-4
36 https://doi.org/10.1084/jem.147.3.882
37 https://doi.org/10.1084/jem.148.3.766
38 https://doi.org/10.1084/jem.153.5.1198
39 https://doi.org/10.1084/jem.177.1.119
40 https://doi.org/10.1084/jem.186.7.1149
41 https://doi.org/10.1084/jem.191.8.1355
42 https://doi.org/10.1146/annurev.immunol.23.021704.115658
43 https://doi.org/10.1146/annurev.immunol.26.021607.090421
44 https://doi.org/10.1146/annurev.iy.13.040195.000521
45 https://doi.org/10.4049/jimmunol.164.12.6252
46 schema:datePublished 2009-04
47 schema:datePublishedReg 2009-04-01
48 schema:description An alphabeta T-cell response depends on the recognition of antigen plus major histocompatibility complex (MHC) proteins by its antigen receptor (TCR). The ability of peripheral alphabeta T cells to recognize MHC is at least partly determined by MHC-dependent thymic selection, by which an immature T cell survives only if its TCR can recognize self MHC. This process may allow MHC-reactive TCRs to be selected from a repertoire with completely random and unbiased specificities. However, analysis of thymocytes before positive selection indicated that TCR proteins might have a predetermined ability to bind MHC. Here we show that specific germline-encoded amino acids in the TCR promote 'generic' MHC recognition and control thymic selection. In mice expressing single, rearranged TCR beta-chains, individual mutation of amino acids in the complementarity-determining region (CDR) 2beta to Ala reduced development of the entire TCR repertoire. Altogether, these results show that thymic selection is controlled by germline-encoded MHC contact points in the alphabeta TCR and indicate that the diversity of the peripheral T-cell repertoire is enhanced by this 'built-in' specificity.
49 schema:genre research_article
50 schema:inLanguage en
51 schema:isAccessibleForFree true
52 schema:isPartOf N325d803c5249417c9363fbd23e63c5a5
53 N730dfca597e747f3a41ecb09f728090c
54 sg:journal.1018957
55 schema:name Germline-encoded amino acids in the αβ T-cell receptor control thymic selection
56 schema:pagination 1043
57 schema:productId N309d4c9785a94800a0edce91d6a40b65
58 N6e6ed3de5efe4a39a1d5da34432c5093
59 N7a397e4e7aa34d2999e201558a808415
60 Nc1ea1ad846d7483391d679d730832eef
61 Nc92f3ca576344f72b036a66a4dd02bf9
62 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017171182
63 https://doi.org/10.1038/nature07812
64 schema:sdDatePublished 2019-04-10T16:28
65 schema:sdLicense https://scigraph.springernature.com/explorer/license/
66 schema:sdPublisher N7169604a31ec4a6eba3469e20aa33074
67 schema:url https://www.nature.com/articles/nature07812
68 sgo:license sg:explorer/license/
69 sgo:sdDataset articles
70 rdf:type schema:ScholarlyArticle
71 N07ffa54e2dad412cb20e8938395815c8 rdf:first sg:person.010157255507.71
72 rdf:rest N4c014040e06b488bbb45fafc83e31dcf
73 N163d3c38a41f42a7aec7966e9b790e2f rdf:first sg:person.01360605223.13
74 rdf:rest N07ffa54e2dad412cb20e8938395815c8
75 N3088a9ad824648c795c5635f2ebddc4d rdf:first sg:person.01064765234.16
76 rdf:rest Nfe31a709d0524e55aa7a6721ffdd7b5f
77 N309d4c9785a94800a0edce91d6a40b65 schema:name nlm_unique_id
78 schema:value 0410462
79 rdf:type schema:PropertyValue
80 N325d803c5249417c9363fbd23e63c5a5 schema:volumeNumber 458
81 rdf:type schema:PublicationVolume
82 N3777114487f24961af48361de49185b0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
83 schema:name Hybridomas
84 rdf:type schema:DefinedTerm
85 N3c61fd5a089e4d4184354bf7def0cb15 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
86 schema:name Amino Acids
87 rdf:type schema:DefinedTerm
88 N4c014040e06b488bbb45fafc83e31dcf rdf:first sg:person.01361470371.87
89 rdf:rest N3088a9ad824648c795c5635f2ebddc4d
90 N4c1e974e6c174dee8ec033d5cb423f49 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
91 schema:name Animals
92 rdf:type schema:DefinedTerm
93 N6bba062ec95045a1960c87e8a63c7299 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name Chimera
95 rdf:type schema:DefinedTerm
96 N6e6ed3de5efe4a39a1d5da34432c5093 schema:name doi
97 schema:value 10.1038/nature07812
98 rdf:type schema:PropertyValue
99 N7169604a31ec4a6eba3469e20aa33074 schema:name Springer Nature - SN SciGraph project
100 rdf:type schema:Organization
101 N730dfca597e747f3a41ecb09f728090c schema:issueNumber 7241
102 rdf:type schema:PublicationIssue
103 N7a397e4e7aa34d2999e201558a808415 schema:name pubmed_id
104 schema:value 19262510
105 rdf:type schema:PropertyValue
106 N811283a4e00d4d55beb0cca00dacbce6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
107 schema:name Bone Marrow
108 rdf:type schema:DefinedTerm
109 N8120fc99467e4565ab7a949a10860779 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Receptors, Antigen, T-Cell, alpha-beta
111 rdf:type schema:DefinedTerm
112 N95458fe7133446efbe8e5f8228381dea schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
113 schema:name Germ Cells
114 rdf:type schema:DefinedTerm
115 Nbd422a56e59b4773a2d757c5473f57de schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
116 schema:name Mice
117 rdf:type schema:DefinedTerm
118 Nbdd5fe47f87b4f37ac54cf36bad49baa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Thymus Gland
120 rdf:type schema:DefinedTerm
121 Nc1ea1ad846d7483391d679d730832eef schema:name readcube_id
122 schema:value 51cf6aaef5d1e1dca0b8a9a7eb13a5d06871aa01fd82acd15b23a4af814d337b
123 rdf:type schema:PropertyValue
124 Nc8c02db41158470ba0e6b224bb45f16e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
125 schema:name Major Histocompatibility Complex
126 rdf:type schema:DefinedTerm
127 Nc92f3ca576344f72b036a66a4dd02bf9 schema:name dimensions_id
128 schema:value pub.1017171182
129 rdf:type schema:PropertyValue
130 Nfa3e5e8c93534f0a806787608cf7d83d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
131 schema:name Cell Line
132 rdf:type schema:DefinedTerm
133 Nfd7b9cd3df9f4eb298a1c331eed74a32 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Complementarity Determining Regions
135 rdf:type schema:DefinedTerm
136 Nfe31a709d0524e55aa7a6721ffdd7b5f rdf:first sg:person.01066606743.28
137 rdf:rest rdf:nil
138 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
139 schema:name Medical and Health Sciences
140 rdf:type schema:DefinedTerm
141 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
142 schema:name Immunology
143 rdf:type schema:DefinedTerm
144 sg:grant.2434864 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
145 rdf:type schema:MonetaryGrant
146 sg:grant.2438855 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
147 rdf:type schema:MonetaryGrant
148 sg:grant.2449844 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
149 rdf:type schema:MonetaryGrant
150 sg:grant.2456456 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
151 rdf:type schema:MonetaryGrant
152 sg:grant.2599494 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
153 rdf:type schema:MonetaryGrant
154 sg:grant.2633733 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
155 rdf:type schema:MonetaryGrant
156 sg:grant.2665697 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
157 rdf:type schema:MonetaryGrant
158 sg:grant.2665703 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
159 rdf:type schema:MonetaryGrant
160 sg:grant.2681866 http://pending.schema.org/fundedItem sg:pub.10.1038/nature07812
161 rdf:type schema:MonetaryGrant
162 sg:journal.1018957 schema:issn 0090-0028
163 1476-4687
164 schema:name Nature
165 rdf:type schema:Periodical
166 sg:person.010157255507.71 schema:affiliation https://www.grid.ac/institutes/grid.241116.1
167 schema:familyName White
168 schema:givenName Janice
169 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010157255507.71
170 rdf:type schema:Person
171 sg:person.01064765234.16 schema:affiliation https://www.grid.ac/institutes/grid.241116.1
172 schema:familyName Gapin
173 schema:givenName Laurent
174 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01064765234.16
175 rdf:type schema:Person
176 sg:person.01066606743.28 schema:affiliation https://www.grid.ac/institutes/grid.430503.1
177 schema:familyName Marrack
178 schema:givenName Philippa
179 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01066606743.28
180 rdf:type schema:Person
181 sg:person.01360605223.13 schema:affiliation https://www.grid.ac/institutes/grid.241116.1
182 schema:familyName Scott-Browne
183 schema:givenName James P.
184 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01360605223.13
185 rdf:type schema:Person
186 sg:person.01361470371.87 schema:affiliation https://www.grid.ac/institutes/grid.413575.1
187 schema:familyName Kappler
188 schema:givenName John W.
189 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01361470371.87
190 rdf:type schema:Person
191 sg:pub.10.1007/bf00172177 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031690752
192 https://doi.org/10.1007/bf00172177
193 rdf:type schema:CreativeWork
194 sg:pub.10.1038/248701a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021418039
195 https://doi.org/10.1038/248701a0
196 rdf:type schema:CreativeWork
197 sg:pub.10.1038/269417a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034526188
198 https://doi.org/10.1038/269417a0
199 rdf:type schema:CreativeWork
200 sg:pub.10.1038/335730a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026925225
201 https://doi.org/10.1038/335730a0
202 rdf:type schema:CreativeWork
203 sg:pub.10.1038/336073a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017494831
204 https://doi.org/10.1038/336073a0
205 rdf:type schema:CreativeWork
206 sg:pub.10.1038/ni1502 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032706930
207 https://doi.org/10.1038/ni1502
208 rdf:type schema:CreativeWork
209 sg:pub.10.1038/ni1510 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010605813
210 https://doi.org/10.1038/ni1510
211 rdf:type schema:CreativeWork
212 sg:pub.10.1038/nri853 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015746364
213 https://doi.org/10.1038/nri853
214 rdf:type schema:CreativeWork
215 sg:pub.10.1186/1471-2105-7-225 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052511038
216 https://doi.org/10.1186/1471-2105-7-225
217 rdf:type schema:CreativeWork
218 https://app.dimensions.ai/details/publication/pub.1079346876 schema:CreativeWork
219 https://doi.org/10.1002/eji.1830010102 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012650964
220 rdf:type schema:CreativeWork
221 https://doi.org/10.1016/0092-8674(86)90591-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1041841357
222 rdf:type schema:CreativeWork
223 https://doi.org/10.1016/j.cell.2005.05.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012919320
224 rdf:type schema:CreativeWork
225 https://doi.org/10.1016/j.immuni.2004.11.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027550001
226 rdf:type schema:CreativeWork
227 https://doi.org/10.1016/j.immuni.2008.01.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026719767
228 rdf:type schema:CreativeWork
229 https://doi.org/10.1016/s0092-8674(00)81905-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041641914
230 rdf:type schema:CreativeWork
231 https://doi.org/10.1016/s0092-8674(85)80103-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046706960
232 rdf:type schema:CreativeWork
233 https://doi.org/10.1016/s1074-7613(00)80523-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052289649
234 rdf:type schema:CreativeWork
235 https://doi.org/10.1016/s1074-7613(00)80547-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033287487
236 rdf:type schema:CreativeWork
237 https://doi.org/10.1016/s1074-7613(04)00378-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1054680329
238 rdf:type schema:CreativeWork
239 https://doi.org/10.1084/jem.147.3.882 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008369492
240 rdf:type schema:CreativeWork
241 https://doi.org/10.1084/jem.148.3.766 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048475518
242 rdf:type schema:CreativeWork
243 https://doi.org/10.1084/jem.153.5.1198 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014615515
244 rdf:type schema:CreativeWork
245 https://doi.org/10.1084/jem.177.1.119 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000666423
246 rdf:type schema:CreativeWork
247 https://doi.org/10.1084/jem.186.7.1149 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003929300
248 rdf:type schema:CreativeWork
249 https://doi.org/10.1084/jem.191.8.1355 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047071681
250 rdf:type schema:CreativeWork
251 https://doi.org/10.1146/annurev.immunol.23.021704.115658 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019295510
252 rdf:type schema:CreativeWork
253 https://doi.org/10.1146/annurev.immunol.26.021607.090421 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004718812
254 rdf:type schema:CreativeWork
255 https://doi.org/10.1146/annurev.iy.13.040195.000521 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045836159
256 rdf:type schema:CreativeWork
257 https://doi.org/10.4049/jimmunol.164.12.6252 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000967261
258 rdf:type schema:CreativeWork
259 https://www.grid.ac/institutes/grid.241116.1 schema:alternateName University of Colorado Denver
260 schema:name Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA
261 rdf:type schema:Organization
262 https://www.grid.ac/institutes/grid.413575.1 schema:alternateName Howard Hughes Medical Institute
263 schema:name Department of Medicine,
264 Department of Pharmacology,
265 Howard Hughes Medical Institute,
266 Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA
267 Program in Biomolecular Structure and,
268 rdf:type schema:Organization
269 https://www.grid.ac/institutes/grid.430503.1 schema:alternateName University of Colorado Anschutz Medical Campus
270 schema:name Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado 80220, USA
271 Department of Medicine,
272 Howard Hughes Medical Institute,
273 Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA
274 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...