| First Author | Chen X | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 11 | Pages | 3417-3433 |
| PubMed ID | 28835417 | Mgi Jnum | J:250249 |
| Mgi Id | MGI:5922908 | Doi | 10.1084/jem.20161784 |
| Citation | Chen X, et al. (2017) Human TCR-MHC coevolution after divergence from mice includes increased nontemplate-encoded CDR3 diversity. J Exp Med 214(11):3417-3433 |
| abstractText | For thymic selection and responses to pathogens, T cells interact through their alphabeta 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. |
