Sequences in both class II major histocompatibility complex alpha and beta chains contribute to the binding of the superantigen toxic shock syndrome toxin 1.

Abstract

Summar~Class II major histocompatibility complex (MFIC) molecules present peptides derived from processed antigen to antigen-specific CD4-positive T cells. In addition, class II molecules bind with high affinity another class of antigens, termed superantigens. T cell stimulation by superantigens depends almost exclusively on the V3 segment expressed by the T ceil receptor (TCR). Mapping of the superantigen binding site on class II molecules should provide valuable information on how MHC and TCR molecules interact. Recombinant mouse I-A class II molecules expressed on transfected L cells were analyzed for their ability to bind the toxic shock syndrome toxin 1. Polymorphic residues in the ol helices of both the ol and B chains of I-A contributed to quantitative toxin binding, suggesting that the toxin binds to either a combinatorial or a conformational site on class II MHC molecules.

Understanding the mechanism of action of bacterial superantigens from a decade of research

“…depends on each SAg(Fig. 2) and raises several important questions on how this relates to their different functional properties.SEB and TSST-1 show prototypic interaction witii MiHC class il moleculesThe mode of interaction of SEB(47)(48)(49) and TSST-1 complexed with the HLA-DR 1(49)(50)(51)(52)(53) is of particular relevance because it illustrates two distinct and functionally important topologies of engagement of the TCR: one which may allow TCR:MHC contacts to occur (39) (as in SEB;Fig. 3A), and the other (i.e.…”

Distinct binding sites on HLA-DR for invariant chain and staphylococcal enterotoxins.

“…This The reduced binding of TSST in the presence of surface Ii provides additional evidence for the distinction among different toxins in the way they interact with class II. SEA and SEE bind to a conserved region in the a-helical portion of the DR /3 chain (18,27), while TSST interacts with sequences in the al domain of DR and in the a-helices of both a and /8 chains in mouse Ia (19,20). However, there may be a degree of overlap among these sites as demonstrated by partial cross-inhibition of binding (28).…”

“…The structurally similar toxins staphylococcal enterotoxins A and E (SEA and SEE) bind to a conserved region of the class II ( chain including the histidine residue at position 81 (17,18). Toxic shock syndrome toxin (TSST) requires sequences in the al domain for high-affinity binding to human class II (19) and in both the al and (31 domains of mouse class II (20). Finally, the residues necessary for binding of antigenic peptides to class II have been shown to be distinct from those involved in toxin binding (21).…”

Evidence for a superantigen in the pathogenesis of tuberculosis

“…3, in vitro stimulation with the M. tuberculosis extracts leads to significant expansion of V/38 + T cells and was always at least two times the level of expansion seen in Superantigens have now been shown by genetic [15], biochemical [36], molecular [19,33,43] and crystalographic [20] techniques to interact with MHC class II molecules away from the peptide-binding groove. Because of this unique interaction with the MHC class II molecule, superantigens are not haplotype restricted (see above), but are absolutely dependent upon MHC class II molecules for their presentation to T cells [9,14,23,24,33,36,40]. To demonstrate formally that the M. tuberculosis superantigen requires MHC class II molecules, T cell lines were set up from normal donors with the M. tuberculosis extract as the stimuli.…”