Evidence for a functional sidedness to the αβTCR

Michael S. Kuhns, Andrew T. Girvin, Lawrence O. Klein, Rebecca Chen, Kirk D.C. Jensen, Evan W. Newell, Johannes B. Huppa, Björn F. Lillemeier, Morgan Huse, Yueh Hsiu Chien, K. Christopher Garcia, Mark M. Davis

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The T cell receptor (TCR) and associated CD3γε, δε, and ζζ signaling dimers allow T cells to discriminate between different antigens and respond accordingly, but our knowledge of how these parts fit and work together is incomplete. In this study, we provide additional evidence that the CD3 heterodimers congregate on one side of the TCR in both the αβ and γδTCR-CD3 complexes. We also report that the other side of the αβTCR mediates homotypic αβTCR interactions and signaling. Specifically, an erythropoietin receptor-based dimerization assay was used to show that, upon complex assembly, the CD3ε chains of two CD3 heterodimers are arranged side-by-side in both the αβ and γδTCR-CD3 complexes. This system was also used to show that αβTCRs can dimerize in the cell membrane and that mutating the unusual outer strands of the Cα domain impairs this dimerization. Finally, we present data showing that, for CD4 T cells, the mutations that impair αβTCR dimerization also alter ligand-induced calcium mobilization, TCR accumulation at the site of pMHC contact, and polarization toward the site of antigen contact. These data reveal a "functional- sidedness" to the αβTCR constant region, with dimerization occurring on the side of the TCR opposite from where the CD3 heterodimers are located.

Original languageEnglish (US)
Pages (from-to)5094-5099
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number11
DOIs
StatePublished - Mar 16 2010
Externally publishedYes

Keywords

  • CD3
  • Dimerization
  • Organization
  • Signaling
  • T cell
  • T cell receptor

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Evidence for a functional sidedness to the αβTCR'. Together they form a unique fingerprint.

Cite this