Evidence for a functional sidedness to the alphabetaTCR.
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.
Kuhns
Michael S
MS
Department of Microbiology and Immunology, Graduate Program in Immunology, The Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Girvin
Andrew T
AT
Klein
Lawrence O
LO
Chen
Rebecca
R
Jensen
Kirk D C
KD
Newell
Evan W
EW
Huppa
Johannes B
JB
Lillemeier
Björn F
BF
Huse
Morgan
M
Chien
Yueh-Hsiu
YH
Garcia
K Christopher
KC
Davis
Mark M
MM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology; D017252:CD3 Complex / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology
D017252:CD3 Complex; D021122:Protein Subunits; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta