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

13 Citations (Scopus)

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

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T-Lymphocyte Epitopes
T-Cell Antigen Receptor
HLA-A2 Antigen
T-Lymphocytes
Peptides
Human Influenza
Antigens
Immunodominant Epitopes
Viral Antigens
Antiviral Agents
Immunity
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope. / Song, In Young; Gil, Anna; Mishra, Rabinarayan; Ghersi, Dario; Selin, Liisa K.; Stern, Lawrence J.

In: Nature Structural and Molecular Biology, Vol. 24, No. 4, 01.04.2017, p. 395-406.

Research output: Contribution to journalArticle

Song, In Young ; Gil, Anna ; Mishra, Rabinarayan ; Ghersi, Dario ; Selin, Liisa K. ; Stern, Lawrence J. / Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope. In: Nature Structural and Molecular Biology. 2017 ; Vol. 24, No. 4. pp. 395-406.
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