Antagonism of cytotoxic T-lymphocyte activation by soluble CD8

The CD8 co-receptor is important in the differentiation and selection of cl ass 1 MHC-restricted 7 cells during thymic development, and in the activati on of mature T lymphocytes in response to antigen. Here we show that solubl e CD8 alpha alpha receptor, despite an extremely low affinity for MHC, inhi bits activation of cytotoxic lymphocytes by obstructing CD3 zeta-chain phos phorylation. We propose a model for this effect that involves interference of productive receptor multimerization at the T-cell surface. These results provide new insights into the mechanism of T-cell activation and evidence that CD8 function is exquisitely sensitive to disruption, an effect that mi ght be exploited by molecular therapeutics.