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Nat Struct Mol Biol. 2017 Apr;24(4):395-406. doi: 10.1038/nsmb.3383. Epub 2017 Feb 27.

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

Author information

1
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
2
Graduate Program in Immunology and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
3
School of Interdisciplinary Informatics, University of Nebraska at Omaha, Omaha, Nebraska, USA.
4
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

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.

PMID:
28250417
PMCID:
PMC5383516
DOI:
10.1038/nsmb.3383
[Indexed for MEDLINE]
Free PMC Article

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