V7, A NOVEL LEUKOCYTE SURFACE PROTEIN THAT PARTICIPATES IN T-CELL ACTIVATION .1. TISSUE DISTRIBUTION AND FUNCTIONAL-STUDIES

Among a panel of mouse mAbs generated to a human T cell clone, one mAb , V7.1, inhibited T cell activation in the mixed lymphocyte reaction a nd was studied further. V7.1 reacted strongly with Ag-specific T cell clones, in addition to freshly isolated monocytes and granulocytes. Ho wever, the mAb reacted weakly with freshly isolated PBLs (T cells, B c ells, and NK cells), T cells stimulated with phytohemagglutinin, or Co n A, and did not stain the vast majority of transformed cell lines of hemopoietic origin. Stimulation of T cells with anti-CD3, or the combi nation of anti-CD3 and PMA, or anti-CD3, PMA and ionomycin, markedly i ncreased V7.1 surface staining. The mAb precipitated a single polypept ide chain of approximately 135 kDa from alloactivated T cells or monoc ytes, which was reduced to approximately 110 kDa after treatment with N-glycanase. The proliferative response of T cells to allogeneic monoc ytes or B lymphoblastoid cells was inhibited by V7.1, and inhibition w as maximal when the mAb was present at the initiation of culture. V7.1 also exhibited dose-dependent inhibition of the T cell response to im mobilized anti-CD3 Ab in the absence of APCs, indicating that the inhi bitory effect of this Ab occurs at the T cell level. Expression of CD2 5 (IL-2R) on anti-CD3-activated T cells and secretion of IL-2 induced with anti-CD3 and PMA were inhibited by V7.1, whereas the Ab had no ef fect on T cell proliferation induced by PHA or Con A or on T cell-medi ated cytotoxicity. These results indicate that V7.1 recognizes a novel leukocyte surface glycoprotein, designated V7, that is up-regulated o n Ag but not lectin-activated T cells, and appears to play a role in T CR/CD3-dependent T cell activation. In an accompanying study, the gene encoding the V7 Ag is described and the molecule is shown to be a nov el member of the Ig superfamily.