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| Item Type: | Article |
|---|---|
| Title: | Human TCR-MHC coevolution after divergence from mice includes increased nontemplate-encoded CDR3 diversity |
| Creators Name: | Chen, X. and Poncette, L. and Blankenstein, T. |
| Abstract: | For thymic selection and responses to pathogens, T cells interact through their {alpha}{beta} T cell receptor (TCR) with peptide-major histocompatibility complex (MHC) molecules on antigen-presenting cells. How the diverse TCRs interact with a multitude of MHC molecules is unresolved. It is also unclear how humans generate larger TCR repertoires than mice do. We compared the TCR repertoire of CD4 T cells selected from a single mouse or human MHC class II (MHC II) in mice containing the human TCR gene loci. Human MHC II yielded greater thymic output and a more diverse TCR repertoire. The complementarity determining region 3 (CDR3) length adjusted for different inherent V-segment affinities to MHC II. Humans evolved with greater nontemplate-encoded CDR3 diversity than did mice. Our data, which demonstrate human TCR-MHC coevolution after divergence from rodents, explain the greater T cell diversity in humans and suggest a mechanism for ensuring that any V-J gene combination can be selected by a single MHC II. |
| Keywords: | Complementarity Determining Regions, Evolution, Molecular, Genetic Variation, HLA Antigens, Major Histocompatibility Complex, Receptors, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Animals, Mice, 129 Strain, Mice, Inbred BALB C, Mice, Inbred C57BL |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 214 |
| Number: | 11 |
| Page Range: | 3417-3433 |
| Date: | 6 November 2017 |
| Official Publication: | https://doi.org/10.1084/jem.20161784 |
| PubMed: | View item in PubMed |
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