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

doi:10.1038/nsmb.3383

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

Biomedical Informatics

Research output: Contribution to journal › Article › peer-review

32 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 language	English (US)
Pages (from-to)	395-406
Number of pages	12
Journal	Nature Structural and Molecular Biology
Volume	24
Issue number	4
DOIs	https://doi.org/10.1038/nsmb.3383
State	Published - Apr 1 2017

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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title = "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.",

author = "Song, {In Young} and Anna Gil and Rabinarayan Mishra and Dario Ghersi and Selin, {Liisa K.} and Stern, {Lawrence J.}",

note = "Funding Information: This work was supported by the NIH (grants AI038996 (to L.J.S.), AI49320 (to L.K.S.), and AI109858 (to L.J.S. and L.K.S.)) and the Nebraska Research Initiative (grant to D.G.). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Publisher Copyright: {\textcopyright} 2017 Nature America, Inc., part of Springer Nature. All rights reserved.",

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AU - Stern, Lawrence J.

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