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

UMMS Affiliation

Department of Pathology; Graduate School of Biomedical Sciences, Immunology and Microbiology Program

Publication Date


Document Type



Biochemistry | Immunology and Infectious Disease | Immunopathology | Molecular Biology | Structural Biology


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.


UMCCTS funding

DOI of Published Version



Nat Struct Mol Biol. 2017 Apr;24(4):395-406. doi: 10.1038/nsmb.3383. Epub 2017 Feb 27. Link to article on publisher's site

Journal/Book/Conference Title

Nature structural and molecular biology


First author InYoung Song is a doctoral student in the Immunology and Microbiology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed

PubMed ID