Evidence for a functional sidedness to the abTCR

• Published in: Proceedings of the National Academy of Sciences - PNAS 2010-01, Vol.107 (11), p.5094-5099
• Main Authors: Kuhns, Michael S, Girvin, Andrew T, Klein, Lawrence O, Chen, Rebecca, Jensen, Kirk DC, Newell, Evan W, Huppa, Johannes B, Lillemeier, Bjoern F, Huse, Morgan, Chien, Yueh-hsiu, Garcia, KChristopher, Davis, Mark M
• Format: Article
• Language: English
• ISSN: 0027-8424
• DOI: 10.1073/pnas.1000925107

The T cell receptor (TCR) and associated CD3gIk, dIk, and II 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 ab and gdTCR-CD3 complexes. We also report that the other side of the abTCR mediates homotypic abTCR interactions and signaling. Specifically, an erythropoietin receptor-based dimerization assay was used to show that, upon complex assembly, the CD3Ik chains of two CD3 heterodimers are arranged side-by-side in both the ab and gdTCR-CD3 complexes. This system was also used to show that abTCRs can dimerize in the cell membrane and that mutating the unusual outer strands of the Ca domain impairs this dimerization. Finally, we present data showing that, for CD4 T cells, the mutations that impair abTCR 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 abTCR constant region, with dimerization occurring on the side of the TCR opposite from where the CD3 heterodimers are located.