Immunogenetic aspects of host immune response.

The central role of histocompatibility leukocyte antigens (HLA) class II molecules in antigen presentation has received great attention in recent years, yet class I molecules have been defined as primarily functioning as a restriction element for cytotoxic T cell killing of virus-infected cells. Extensive clinical evidence, however, indicates that the HLA class I genes are strongly associated with nonseptic complications of enteric and genitourinary bacterial infections. Ninety percent of patients with Reiter's syndrome and reactive arthritis are positive for HLA-B27, yet the mechanism of disease susceptibility conferred by this gene remains obscure. Hypotheses concerning this interaction include (i) class I antigens functioning as receptors for microbial antigens; (ii) class I antigens expressing determinants that cross-react with microbial antigens; and (iii) class I genes controlling immunoregulatory functions that dictate qualitative differences in immune response to pathogenic organisms. These hypotheses await formal testing and hold great promise for understanding immunogenetic control of immune responses in general.