T Cell Receptor - independent CD 2 Signal Transduction in FcR + Cells By Antonio

CD2 subserves both adhesion and signal transduction functions in T cells, thymocytes, and natural killer (NK) cells. In mature T lymphocytes, CD2-mediated signaling function apparently requires surface expression of T cell receptors (TCRs) . In contrast, in CD2+CD3NK cells and thymocytes, signal transduction through CD2 is TCR independent . To resolve this paradox and characterize TCR-independent triggering mechanisms, we transfected a human CD2 cDNA into a murine mast cell line, C1.MC/57 (Fcc-Rl+, FcyRII+, FcyRIII+), which is known to produce interleukin 6 (IL6) as well as release histamine in response to crosslinking of FceRI . In the CD2 transfectant, a combination of antiT112 + antiT113 monoclonal antibodies (mAbs) induced a rise in intracellular free calcium ([Ca2 +]i), 11,6 production, and histamine release . As expected, no activation was mediated by the same mAbs in C1.MC/57 . F(ab)'2 fragments of the activatory combination of antiT112 + antiT113 mAbs induced IL-6 in the CD2-transfected mast cells, demonstrating an Fcy receptor ectodomain-independent triggering mechanism . In addition, either intact anti-T112 or anti-T113 IgG alone, which failed to induce [Ca2+]i mobilization in the transfectant, was able to induce IL6 production . A mAb directed against both FcyRII (previously denoted as Fc-yRIIb) and FcyRIII (previously denoted as FcTRIIa) inhibits this induction . These results indicate that : (a) Cat+ mobilization is not essential for IL6 production ; and (b) crosslinking of CD2 and Fcy receptors via intact anti-CD2 IgG stimulates 11,6 production . Thus, CD2-mediated IL6 production occurs by both Fc receptor ectodomain-independent as well as Fc receptor ectodomain-dependent mechanisms in these nonlymphoid cells . Northern blot analysis demonstrates that although the mast cells do not express CD31' or CD3vl mRNA, they express Fcc-RIy mRNA. The latter is a known component of FcyRIII as well as FceRI, has significant homology to CD31'/t, and is thought to have a signal transduction function . In these mast cells, CD2 signaling machinery does not require CD31'/rl and may be linked to the Fcc-RIy subunit . We predict that this subunit or a related structure may confer a TCR-independent signal transduction pathway upon CD2 in CD3NK cells, thymocytes, and certain B lymphocytes .