Transgenic mice with a diverse human T cell antigen receptor repertoire View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-09

AUTHORS

Liang-Ping Li, J Christoph Lampert, Xiaojing Chen, Catarina Leitao, Jelena Popović, Werner Müller, Thomas Blankenstein

ABSTRACT

Because of tolerance mechanisms, it has been hard to identify the T cell receptors (TCRs) of high-avidity T cells against self (for example, tumor) antigens. TCRs that are specific for foreign human antigens from the nontolerant T cell repertoire can be identified in mice. Moreover, if mice are constructed to express the human TCR repertoire, they can be used to analyze the unskewed repertoire against human self antigens. Here we generated transgenic mice with the entire human TCRalphabeta gene loci (1.1 and 0.7 Mb), whose T cells express a diverse human TCR repertoire that compensates for mouse TCR deficiency. A human major histocompatibility class I transgene increases the generation of CD8+ T cells with human compared to mouse TCRs. Functional CD8+ T cells against several human tumor antigens were induced, and those against the Melan-A melanoma antigen used similar TCRs to those that have been detected in T cell clones from individuals with autoimmune vitiligo or melanoma. These mice will allow researchers to identify pathogenic and therapeutic human TCRs. More... »

PAGES

1029

Journal

TITLE

Nature Medicine

ISSUE

9

VOLUME

16

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.2197

DOI

http://dx.doi.org/10.1038/nm.2197

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1027194388

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20693993


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