Jay S. Markowitz

Immunoregulatory effects of superantigens : interactions of staphylococcal enterotoxins with host MHC and non-MHC products

Staphylococcus aureus carries a highly conserved set of genes which encode a set of secreted enterotoxins. Although it is likely that these enterotoxins affect the host/parasite in favor of the bacterium, we do not understand the molecular basis of this interaction. We summarize recent evidence that defines two types of interaction between the bacterial toxin and host cellular receptors that may subvert the host immune response to S. aureus. An interaction between the toxin and class II products on APC can result in inhibition of costimulatory activity and thus impair clonal expansion of T cells specific for bacterial antigens. Studies using anti-class II antibodies suggest that this may reflect transmission of a negative signal to APC after ligation of class II products. A second interaction between a subset of toxins, including SEC, with non-MHC products stimulates both T-cell proliferation as well as toxin-specific cytotoxic T cells (CTL). We put forward the hypothesis that this interaction reflects binding of a VCAM-1-like subsequence of SEC to VLA-4 expressed by activated target cells. We suggest that this interaction may serve to inhibit the host response by subversion of lymphocyte homing to sites of infection by SEC-producing staphylococci and by local elimination of (VLA-4+) memory T cells.

MHC Class II Mutant Mice

Publisher Summary Major histocompatibility complex (MHC) class II molecules are polymorphic antigens encoded by four gene loci in the mouse: A α , A β , E α , and E β . Non-covalent association of appropriate α and β chains results in the stable cell surface expression of the two isotypic forms: I-A and I-E. In contrast to the ubiquitous expression of MHC class I antigens, class II molecules are expressed only on B lymphocytes, a subset of macrophages, dendritic cells, and thymic epithelium. Despite their limited tissue distribution, MHC class II molecules are critical to the initiation and maintenance of many types of immune responses. The present study uses the approach of gene targeting in embryonic stem (ES) cells to generate animals that are deficient in their cell surface expression of MHC class II molecules. These MHC class II mutant mice have proved to be valuable reagents for addressing the mechanisms governing the development and function of cells in the immune system.