Identification of the staphylococcal enterotoxin A superantigen binding site in the beta 1 domain of the human histocompatibility antigen HLA-DR.

Abstract

The staphylococcal enterotoxin A (SEA) is a superantigen that must bind to class II molecules of the major histocompatibility complex to be recognized by T cells. In humans, most HLA-DR class II allelic and isotypic forms, such as DR1, bind SEA well. DRw53 is an exception, binding SEA very poorly. We have localized this difference to a single residue (amino acid 81) in the fl1 domain. A highly conserved histidine at residue 81 allows SEA binding, but a tyrosine does not. Residue 81 is predicted to lie in an a-helix on the surface of the molecule, with its side chain pointing up out of the pocket associated with binding of conventional peptide antigens. This rinding supports the hypothesis that superantigens and conventional antigens bind to different sites on the class II molecule.Recently, a class of antigens has been characterized that stimulates T cells predominantly through the 13chain variable region element of the T-cell receptor (1-3). They differ from conventional peptide antigens, which require specific interaction with several variable elements of the T-cell receptor (4, 5). These molecules have been termed superantigens, since they stimulate large numbers of T cells (2). The superantigen family includes mouse self superantigens encoded by mouse mammary tumor viruses (6-8) and a number of microbial exotoxins implicated in severe shock-like disorders. Among the best characterized superantigens are the staphylococcal exotoxins, a family of basic secretory proteins of 22-30 kDa such as the staphylococcal enterotoxins (SEs) SEA, SEB, SEC1-3, SED, and SEE and the toxic shock syndrome toxin (9-11).Superantigen binding to major histocompatibility complex (MHC) class II molecules is a prerequisite for T-cell stimulation (2,(12)(13)(14) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells

“…It is unlikely that costimulation influences allo-antigen and superantigen reactivity, but reports have demonstrated that a cell's peptide repertoire can influence allogeneic T-cell responses and superantigen binding. 63,64 Invariant chain and DM activity determine the peptide repertoire and, in turn, the cell's ability to present superantigen and elicit allogeneic responses. 65 Therefore, it remains possible that CVEs have altered invariant chain and DM activity that influence their peptide repertoire, affecting their ability to elicit alloreactivity and to bind superantigen.…”

Characterization and biological properties of a new staphylococcal exotoxin.

“…Each member has its unique biochemical and serological properties, but shares significant homology in sequence, structure, and biological functions with other family members (1,6). Staphylococcal enterotoxins are also characterized as "superantigens" with all members activating large numbers of T cells bearing particular TCR V~ elements (7)(8)(9). As a result of T cell activa-1 Abbreviations used in this paper: FPLC, fast protein liquid chromatography; LB, Luria-Bertani medium; pI, isoelectric point; SEA, SEB, SEC1, SEE, staphylococcal enterotoxins A, B, C1, D, and E, respectively; TSS, toxic shock syndrome; TSST-1, TSS toxin 1. tion, T cell proliferation and cytokine expression are profoundly elevated.…”

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

“…The binding sites for several staphylococcal toxins have been identified. 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).…”