Cytokine induction by mycoplasma arthritidis-derived superantigen (MAS), but not by TSST-1 or SEC-3, is correlated to certain HLA-DR types

Abstract

Superantigens bind to major histocompatibility complex (MHC) class II molecules on antigen presenting cells and T cells in a Vβ-restricted manner. Both cell types are activated resulting in cytokine production. Although the MHC-II binding site for superantigens has been well described, little is known as to whether this binding complex has an influence on cytokine induction. In order to assess superantigen induced cytokine production and its correlation to HLA-DR types, the authors stimulated peripheral blood from 40 subjects with superantigens toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin C-3 (SEC-3) and Mycoplasma arthritidis-derived superantigen (MAS), and measured cytokine levels thereafter. The HLA-DR type was determined in each subject. A statistical evaluation was carried out between the highest superantigen cytokine induction and the presence of certain HLA-DR types. Whereas MAS presented a statistical association between the highest cytokine production with HLA-DR4, DR7 and DR12, no such associations were observed for TSST-1 and SEC-3. These results demonstrate that T cell stimulation, and consequently its cytokine production by MAS but not by TSST-1 and SEC-3, depends on the presenting HLA-DR type. Because the diverse HLA-DR specificities are given according to the variability of the β chain of the HLA-DR molecule, the data suggest the participation of the human MHC-II β chain in the MAS/MHC-II binding.