| First Author | Logunova NN | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 24 | Pages | 13659-13669 |
| PubMed ID | 32482872 | Mgi Jnum | J:290794 |
| Mgi Id | MGI:6436756 | Doi | 10.1073/pnas.2003170117 |
| Citation | Logunova NN, et al. (2020) MHC-II alleles shape the CDR3 repertoires of conventional and regulatory naive CD4(+) T cells. Proc Natl Acad Sci U S A 117(24):13659-13669 |
| abstractText | T cell maturation and activation depend upon T cell receptor (TCR) interactions with a wide variety of antigenic peptides displayed in a given major histocompatibility complex (MHC) context. Complementarity-determining region 3 (CDR3) is the most variable part of the TCRalpha and -beta chains, which govern interactions with peptide-MHC complexes. However, it remains unclear how the CDR3 landscape is shaped by individual MHC context during thymic selection of naive T cells. We established two mouse strains carrying distinct allelic variants of H2-A and analyzed thymic and peripheral production and TCR repertoires of naive conventional CD4(+) T (Tconv) and naive regulatory CD4(+) T (Treg) cells. Compared with tuberculosis-resistant C57BL/6 (H2-A(b)) mice, the tuberculosis-susceptible H2-A(j) mice had fewer CD4(+) T cells of both subsets in the thymus. In the periphery, this deficiency was only apparent for Tconv and was compensated for by peripheral reconstitution for Treg We show that H2-A(j) favors selection of a narrower and more convergent repertoire with more hydrophobic and strongly interacting amino acid residues in the middle of CDR3alpha and CDR3beta, suggesting more stringent selection against a narrower peptide-MHC-II context. H2-A(j) and H2-A(b) mice have prominent reciprocal differences in CDR3alpha and CDR3beta features, probably reflecting distinct modes of TCR fitting to MHC-II variants. These data reveal the mechanics and extent of how MHC-II shapes the naive CD4(+) T cell CDR3 landscape, which essentially defines adaptive response to infections and self-antigens. |
