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Human TCR-MHC coevolution after divergence from mice includes increased nontemplate-encoded CDR3 diversity

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Official URL:https://doi.org/10.1084/jem.20161784
PubMed:View item in PubMed
Creators Name:Chen, X. and Poncette, L. and Blankenstein, T.
Journal Title:Journal of Experimental Medicine
Journal Abbreviation:J Exp Med
Date:23 August 2017
Keywords:Animals, Mice
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.
Publisher:Rockefeller University Press (U.S.A.)
Item Type:Article

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