Ontology type: schema:ScholarlyArticle Open Access: True
2019-12
AUTHORSJinghua Lu, François Van Laethem, Abhisek Bhattacharya, Marco Craveiro, Ingrid Saba, Jonathan Chu, Nicholas C. Love, Anastasia Tikhonova, Sergei Radaev, Xiaoping Sun, Annette Ko, Tomer Arnon, Eric Shifrut, Nir Friedman, Nan-Ping Weng, Alfred Singer, Peter D. Sun
ABSTRACTThe αβ T cell receptor (TCR) repertoire on mature T cells is selected in the thymus, but the basis for thymic selection of MHC-restricted TCRs from a randomly generated pre-selection repertoire is not known. Here we perform comparative repertoire sequence analyses of pre-selection and post-selection TCR from multiple MHC-sufficient and MHC-deficient mouse strains, and find that MHC-restricted and MHC-independent TCRs are primarily distinguished by features in their non-germline CDR3 regions, with many pre-selection CDR3 sequences not compatible with MHC-binding. Thymic selection of MHC-independent TCR is largely unconstrained, but the selection of MHC-specific TCR is restricted by both CDR3 length and specific amino acid usage. MHC-restriction disfavors TCR with CDR3 longer than 13 amino acids, limits positively charged and hydrophobic amino acids in CDR3β, and clonally deletes TCRs with cysteines in their CDR3 peptide-binding regions. Together, these MHC-imposed structural constraints form the basis to shape VDJ recombination sequences into MHC-restricted repertoires. More... »
PAGES1019
http://scigraph.springernature.com/pub.10.1038/s41467-019-08906-7
DOIhttp://dx.doi.org/10.1038/s41467-019-08906-7
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