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Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope.


ABSTRACT: A keystone of antiviral immunity is CD8+ T cell recognition of viral peptides bound to MHC-I proteins. The recognition modes of individual T cell receptors (TCRs) have been studied in some detail, but the role of TCR variation in providing a robust response to viral antigens is unclear. The influenza M1 epitope is an immunodominant target of CD8+ T cells that help to control influenza in HLA-A2+ individuals. Here we show that CD8+ T cells use many distinct TCRs to recognize HLA-A2-M1, which enables the use of different structural solutions to the problem of specifically recognizing a relatively featureless peptide antigen. The vast majority of responding TCRs target a small cleft between HLA-A2 and the bound M1 peptide. These broad repertoires lead to plasticity in antigen recognition and protection against T cell clonal loss and viral escape.

SUBMITTER: Song I 

PROVIDER: S-EPMC5383516 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8<sup>+</sup> T cell epitope.

Song InYoung I   Gil Anna A   Mishra Rabinarayan R   Ghersi Dario D   Selin Liisa K LK   Stern Lawrence J LJ  

Nature structural & molecular biology 20170227 4


A keystone of antiviral immunity is CD8<sup>+</sup> T cell recognition of viral peptides bound to MHC-I proteins. The recognition modes of individual T cell receptors (TCRs) have been studied in some detail, but the role of TCR variation in providing a robust response to viral antigens is unclear. The influenza M1 epitope is an immunodominant target of CD8<sup>+</sup> T cells that help to control influenza in HLA-A2<sup>+</sup> individuals. Here we show that CD8<sup>+</sup> T cells use many dist  ...[more]

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