MHC CLASS-II LIGATION INDUCES CD58 (LFA-3)-MEDIATED ADHESION IN HUMANT-CELLS

MHC class II positive T cells found in areas of inflammation are belie ved to play an important pathogenetic role in autoimmunity. In experim ental models, class II molecules have been shown to regulate adhesion between human T cells. It is, however, not known in detail how class I I molecules are functionally linked to adhesion molecules. Some data s uggest that beta(2) integrin (CD11a/CD18) molecules play a role in cla ss-II-induced homotypic adhesion in B cells, monocytes, and virus-tran sformed or neoplastic cell lines. We have previously obtained evidence that adhesion molecules other than beta(2) integrins might play a rol e in class-II-mediated adhesion in T cells. To study further class-II- mediated adhesion in T cells, we have taken advantage of (allo)antigen -specific beta(2)-integrin-negative, CD4-positive T cell lines obtaine d from a leukocyte adhesion deficiency patient. We show that class II ligation induces homotypic adhesion in both beta(2)-integrin-positive and negative, CD4-positive T cell lines. Anti-CD18 monoclonal antibody (mAb) weakly inhibited the adhesion response in beta(2)-integrin-posi tive T cells and had no effect on beta(2)-integrin-negative T cells. I n contrast, an anti-CD58 (LFA-3) mAb almost completely inhibited the a dhesion response in beta(2)-integrin-negative T cells. Antibodies agai nst the CD58 ligand, CD2, partly inhibited the adhesion response in be ta(2)-integrin-negative T cells whereas antibodies against other adhes ion molecules did not. The adhesion response in beta(2)-integrin-posit ive T cells was partly inhibited by antibodies against CD58 and CD2. T aken together, these data provide the first evidence that CD58 molecul es are involved in class-II-induced homotypic adhesion between T cells .