Tyrosine phosphorylation of scavenger receptor cysteine-rich WC1 is required for the WC1-mediated potentiation of TCR-induced T-cell proliferation.
Workshop cluster 1 (WC1) molecules are transmembrane glycoproteins uniquely expressed by gammadelta T cells. They belong to the scavenger receptor cysteine-rich superfamily and are encoded by a multi-gene family, which is divided on the basis of antibody reactivity, into three groups, WC1.1, WC1.2, and WC1.3. The potential role of WC1 as a co-stimulatory molecule for the gammadelta TCR is suggested by the presence of several tyrosine-based motifs in their intracellular domains. In this study, we found that WC1 was constitutively phosphorylated in ex vivo bovine gammadelta T cells and associated with src family tyrosine kinases. Crosslinking of WC1 molecules resulted in an increase in WC1 phosphorylation and co-crosslinking of WC1 and gammadelta TCR together prolonged WC1 phosphorylation. We identified the second tyrosine residue as the primary phosphorylation target in WC1.1 and WC1.2 intracellular sequences in both in vitro and in vivo assays. The cytoplasmic tails of WC1.1 and WC1.2 were phosphorylated on serine and PKC activity was required for PMA-induced endocytosis of WC1.1 or WC1.2. We found that phosphorylation of the second tyrosine in the WC1 cytoplasmic domain was required for the WC1-mediated potentiation of TCR-induced T-cell proliferation, suggesting that WC1 acts as a co-stimulatory molecule for gammadelta TCR.
Wang
Fei
F
Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA, USA.
Herzig
Carolyn
C
Ozer
Dar
D
Baldwin
Cynthia L
CL
Telfer
Janice C
JC
D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
C086500:DMBT1 protein, Bos taurus; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D019061:src-Family Kinases