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

In Young Song, Anna Gil, Rabinarayan Mishra, Dario Ghersi, Liisa K. Selin, Lawrence J. Stern

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)395-406
Number of pages12
JournalNature Structural and Molecular Biology
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2017

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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