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Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5094-9. doi: 10.1073/pnas.1000925107. Epub 2010 Mar 2.

Evidence for a functional sidedness to the alphabetaTCR.

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1
Department of Microbiology and Immunology, Graduate Program in Immunology, The Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Abstract

The T cell receptor (TCR) and associated CD3gammaepsilon, deltaepsilon, and zetazeta 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 alphabeta and gammadeltaTCR-CD3 complexes. We also report that the other side of the alphabetaTCR mediates homotypic alphabetaTCR interactions and signaling. Specifically, an erythropoietin receptor-based dimerization assay was used to show that, upon complex assembly, the CD3epsilon chains of two CD3 heterodimers are arranged side-by-side in both the alphabeta and gammadeltaTCR-CD3 complexes. This system was also used to show that alphabetaTCRs can dimerize in the cell membrane and that mutating the unusual outer strands of the Calpha domain impairs this dimerization. Finally, we present data showing that, for CD4 T cells, the mutations that impair alphabetaTCR 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 alphabetaTCR constant region, with dimerization occurring on the side of the TCR opposite from where the CD3 heterodimers are located.

PMID:
20202921
PMCID:
PMC2841884
DOI:
10.1073/pnas.1000925107
[Indexed for MEDLINE]
Free PMC Article
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