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 coactivating signals to mature T lymphocytes. Studies using monoclonal antibodies (mAb) have defined at least four epitopes on CD6, and distinct functional responses are elicited by mAb to the different epitopes. The function of CD6 is unknown. Multiple CD6 ligands are predicted, based on data that a soluble CD6 fusion protein precipitates at least three peptides. A cDNA clone for one of these ligands, termed activated leucocyte-cell adhesion molecule (ALCAM) has recently been isolated. In order to further characterize the role of CD6 in cell-cell interactions, we have examined the role of CD6 in a variety of responses by tetanus toxoid (TT) specific human T-cell clones. Anti-CD6 mAb UMCD6 (epitope 3) inhibits antigen-specific responses of such clones to TT, but not to the superantigen SEA. Responses of clones to nominal antigen are CD6-dependent using either peripheral blood mononuclear cells (PBMC) or macrophage-depleted E rosette negative cells as the antigen-presenting cell (APC) population. Furthermore, these clones made autoreactive with DNA methyltransferase inhibitors express increased CD6, and autoreactivity is inhibited by UMCD6. Taken together, the data suggests the existence of a functional CD6 ligand in peripheral blood which is expressed by APC, including cells other than macrophages. Interactions between CD6 and CD6 ligands may regulate both antigen specific and autoreactive responses of human T lymphocytes.