Soluble CD8 stabilizes the HLA class I molecule by promoting beta M-2 exchange - Analysis in real-time

Human soluble CD8 (sCD8) is secreted by activated CD8(+) cytotoxic T lympho cytes (CTLs), The immunological role of sCDS is poorly defined, however. We have studied the influence of sCD8 on HLA class I interactions by real-tim e analysis. Using an optical biosensor we demonstrated that the binding of sCD8 to HLA-AZ promotes exchange of beta(2)-microglobulin beta(2)m in order to stabilize the complex. Kinetic analysis showed that sCD8 significantly increased the affinity (K-A) of HLA-A2 for immobilized human beta(2)m,; fro m 1.14 0.04? x 10(9) M-1 in its absence, to 2.18 +/- 0.21 x 109 M-1 followi ng preincubation with sCD8. This suggests that the sCDS:HLA class I complex is unlikely to be degraded at the cell surface. Even in the presence of ex ogenous peptide (HLA-A2 specific or nonspecific), sCDS has a stabilizing in fluence on the HLA class I molecule. These findings point to an immunosuppr essive role for sCD8, because the binding of sCDS to HLA class I would bloc k the binding site for CTL-bound CBS and, therefore, interfere with T cell activation and proliferation. This may have particular significance in path ological situations where elevated levels of sCDS are found in extracellula r fluids, and sCD8 may provide an alternative approach for immunosuppressiv e therapy. (C) American Society for Histocompatibility and Immunogenetics, 1999. Published by Elsevier Science Inc.