ROLE OF THE CD6 GLYCOPROTEIN IN ANTIGEN-SPECIFIC AND AUTOREACTIVE RESPONSES OF CLONED HUMAN T-LYMPHOCYTES

CD6 is a 130 000 MW T-cell surface glycoprotein that can deliver coact ivating signals to mature T lymphocytes. Studies using monoclonal anti bodies (mAb) have defined at least four epitopes on CD6, and distinct functional responses are elicited by mAb to the different epitopes. Th e function of CD6 is unknown. Multiple CD6 ligands are predicted, base d on data that a soluble CD6 fusion protein precipitates at least thre e peptides. A cDNA clone for one of these ligands, termed activated le ucocyte-cell adhesion molecule (ALCAM) has recently been isolated. In order to further characterize the role of CD6 in cell-cell interaction s, we have examined the role of CD6 in a variety of responses by tetan us toroid (TT) specific human T-cell clones. Anti-CD6 mAb UMCD6 (epito pe 3) inhibits antigen-specific responses of such clones to TT, but no t to the superantigen SEA. Responses of clones to nominal antigen are CD6-dependent using either peripheral blood mononuclear cells (PBMC) o r macrophage-depleted E rosette negative cells as the antigen-presenti ng cell (APC) population. Furthermore, these clones made autoreactive with DNA methyltransferase inhibitors express increased CD6, and autor eactivity is inhibited by UMCD6. Taken together, the data suggests the existence of a functional CD6 ligand in peripheral blood which is exp ressed by APC, including cells other than macrophages. Interactions be tween CD6 and CD6 ligands may regulate both antigen specific and autor eactive responses of human T lymphocytes.