Inhibitory effects of anti-HLA-A, B, C heavy chain and anti-beta 2 microglobulin monoclonal antibodies on alloantigen and microbial antigen-induced immune responses in vitro

Abstract

The role of HLA class I subunits in class II-restricted immune responses was investigated by means of a panel of monoclonal antibodies (MoAb) recognizing HLA-A,B,C heavy chain and different beta 2 microglobulin (beta 2m) epitopes. MoAb against either class I subunit strongly inhibited mixed lymphocyte cultures, generation of cytotoxic T lymphocyte cultures, generation of cytotoxic T lymphocytes or natural killer-like activity, and lymphoproliferation in response to soluble or particulate microbial antigens derived from Candida albicans. In general, anti-beta 2m MoAb were more efficient inhibitors than anti-HLA-A,B,C heavy chain MoAb. The inhibitory effects were specific, in that the parental myeloma ascitic fluid or a low-affinity MoAb against beta 2m, or MoAb directed against non-HLA surface structures did not affect any of the immune responses studied. The MoAb-induced inhibition could not be attributed to nonspecific toxic effects, since PHA-induced blastogenesis and IL-2-dependent proliferation of mixed lymphocyte culture (MLC) blasts were not inhibited. Furthermore, exogenous IL-2 did not reverse the block of MLC and microbial antigen-induced proliferative responses by MoAb. Taken together, these data suggest an involvement of both subunits of class I antigens in class II-restricted immune responses.