1342 RE - EVALUATION OF HLA CYTOTOXlCITY INHIBITION

Cross-reactions between mammalian transplantation antigens and certain bacterial structures have been postulated on the basis of various observations. In a series of convincing experiments, Rapaport and Chase (1-3) have clearly demonstrated that skin graft sensitization may be achieved with streptococcal membrane antigens in a variety of different species, such as guinea pigs, mice, rats, or rabbits (4). However, it has been difficult to determine from these experiments whether the observed sensitization was related to antigenic similarities between the bacterial membranes and organ-related transplantation antigens or to products of the major histocompatibility complex (HLA) itself. Therefore, the intriguing question remained: namely, did cross-reactivity between streptococcal antigens and mammalian tissues extend to the individual HLA antigens? The only direct evidence for this possibility has come from HLA cytotoxicity inhibition studies with bacterial structures. In spite of substantial efforts in this direction (5), such studies have remained ambiguous. For example, nonserological inhibitory mechanisms have been suggested (6) while in other experiments specific antibody other than anti-HLA was not strictly excluded (7). In view of these discrepancies, the true nature of the observed inhibition phenomena had to be re-examined before any conclusions about antigenic relationships between histocompatibility antigens and bacterial structures could be drawn. For this purpose, the HLA studies were repeated with the proper controls. The present report indicates that there is no evidence for a serological cross-reaction between streptococcal membrane antigens and the HLA antigens. Rather, the observed inhibitory effect appears to be based on a nonspecific anticomplementary activity of these bacterial structures.