CD59 COSTIMULATION OF T-CELL ACTIVATION - CD58 DEPENDENCE AND REQUIREMENT FOR GLYCOSYLATION

In addition to the TCR-CD3 complex, T lymphocytes can be activated via another surface glycoprotein, the CD2 molecule. CD58 is the principal ligand for human CD2; CD59 and CD48 are two additional, low affinity ligands that have been defined for CD2. In this study, we have explore d the role of CD59 in T cell activation. We have expressed human rCD58 and rCD59 molecules in Chinese hamster oocytes (CHO), and tested para formaldehyde-treated transfectants for the ability to promote prolifer ation of and IL-2 secretion from PBMC and human purified T cells. We h ave shown that CD59 enhanced CD58-dependent T cell proliferation and I L-2 secretion in the presence of suboptimal concentration of PHA or a submitogenic combination of stimulatory anti-CD2 mAbs, T11-2 + T11-3. CD59-dependent costimulation was dependent on several factors includin g the level of coexpression of CD58, the ratio of CHO cell transfectan ts to T cells added in culture, the concentration of mitogen, and also donor-dependent differences. As expected, CD59 costimulation of CD58- dependent T cell proliferation was inhibited by Abs directed against C D59, CD58, and CD2. In our hands, the CD59 molecule itself, in the abs ence of CD58, was unable to support proliferation alone even in the pr esence of exogenous recombinant IL-1, IL-2, or IL-6. Finally, the abil ity of CD59 to enhance CD58-dependent T cell responses was shown to be dependent on N-glycosylation of CP59 at amino acid Asn18.