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MHC-II alleles shape the CDR3 repertoires of conventional and regulatory naive CD4+ T cells.


ABSTRACT: 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 TCR? and -? 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 naïve T cells. We established two mouse strains carrying distinct allelic variants of H2-A and analyzed thymic and peripheral production and TCR repertoires of naïve conventional CD4+ T (Tconv) and naïve regulatory CD4+ T (Treg) cells. Compared with tuberculosis-resistant C57BL/6 (H2-Ab) mice, the tuberculosis-susceptible H2-Aj 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-Aj favors selection of a narrower and more convergent repertoire with more hydrophobic and strongly interacting amino acid residues in the middle of CDR3? and CDR3?, suggesting more stringent selection against a narrower peptide-MHC-II context. H2-Aj and H2-Ab mice have prominent reciprocal differences in CDR3? and CDR3? 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 naïve CD4+ T cell CDR3 landscape, which essentially defines adaptive response to infections and self-antigens.

SUBMITTER: Logunova NN 

PROVIDER: S-EPMC7306996 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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MHC-II alleles shape the CDR3 repertoires of conventional and regulatory naïve CD4<sup>+</sup> T cells.

Logunova Nadezhda N NN   Kriukova Valeriia V VV   Shelyakin Pavel V PV   Egorov Evgeny S ES   Pereverzeva Alina A   Bozhanova Nina G NG   Shugay Mikhail M   Shcherbinin Dmitrii S DS   Pogorelyy Mikhail V MV   Merzlyak Ekaterina M EM   Zubov Vasiliy N VN   Meiler Jens J   Chudakov Dmitriy M DM   Apt Alexander S AS   Britanova Olga V OV  

Proceedings of the National Academy of Sciences of the United States of America 20200601 24


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 TCRα and -β 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 naïve T cells. We established two mouse stra  ...[more]

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