The Journal of Immunology, Vol 147, Issue 11 3876-3881, Copyright © 1991 by American Association of Immunologists

ARTICLES

Staphylococcal toxins bind to different sites on HLA-DR

MM Chintagumpala, JA Mollick and RR Rich
Howard Hughes Medical Institute Laboratory, Baylor College of Medicine, Houston, TX 77030-3498.

Staphylococcal enterotoxins (SE) and toxic shock syndrome toxin 1 (TSST- 1) bind to MHC class II molecules and the toxin-class II complexes induce proliferation of T cells bearing specific V beta sequences. We have previously reported that these toxins display varying binding affinities for HLA-DR1. We now investigated whether these differences simply reflected differences in binding affinity for a single class II binding site or, at least in part, the engagement of different binding sites on the HLA-DR complex. Through competitive binding studies we show that SEB and TSST-1, which are not closely related by their amino acid sequences, bind to two different sites on HLA-DR. Both of these sites are also occupied by staphylococcal enterotoxin A (SEA), enterotoxin D (SED), and enterotoxin E (SEE) which exhibit more than 70% amino acid sequence homology. SEB and TSST-1 failed to inhibit SEA binding to HLA-DR. These studies suggest that there may be three distinct, although perhaps overlapping, binding sites on HLA-DR for these toxins. Further, although SED and SEE are similar to SEA in structure, and appear to bind the same sites on HLA-DR as SEA, they displayed significantly lower binding affinities. T cell proliferative responses to SED required a higher concentration of the toxin than SEA, probably reflecting its lower binding affinity. SEE, however, elicited T cell responses at very low concentrations, similar to SEA, despite its much lower binding affinity. Therefore, although the affinities of these toxins to MHC class II molecules appear to significantly influence the T cell responses, the effective recognition of the toxin- class II complex by the TCR may also contribute to such responses.

This article has been cited by other articles:

				H. Nilsson, P. Bjork, M. Dohlsten, and P. Antonsson Staphylococcal Enterotoxin H Displays Unique MHC Class II-Binding Properties J. Immunol., December 15, 1999; 163(12): 6686 - 6693. [Abstract] [Full Text] [PDF]

				W. Mahana Mapping of Staphylococcal Enterotoxin A Functional Binding Sites and Presentation by Monoclonal Antibodies and Fusion Proteins Infect. Immun., April 1, 1999; 67(4): 1894 - 1900. [Abstract] [Full Text] [PDF]

				L. Leder, A. Llera, P. M. Lavoie, M. I. Lebedeva, H. Li, R.-P. Sekaly, G. A. Bohach, P. J. Gahr, P. M. Schlievert, K. Karjalainen, et al. A Mutational Analysis of the Binding of Staphylococcal Enterotoxins B and C3 to the T Cell Receptor beta  Chain and Major Histocompatibility Complex Class II J. Exp. Med., March 16, 1998; 187(6): 823 - 833. [Abstract] [Full Text] [PDF]

				J. G. Lamphear, K. R. Stevens, and R. R. Rich Intercellular Adhesion Molecule-1 and Leukocyte Function-Associated Antigen-3 Provide Costimulation for Superantigen-Induced T Lymphocyte Proliferation in the Absence of a Specific Presenting Molecule J. Immunol., January 15, 1998; 160(2): 615 - 623. [Abstract] [Full Text] [PDF]

				R. Al-Daccak, K. Mehindate, F. Damdoumi, P. Etongue-Mayer, H. Nilsson, P. Antonsson, M. Sundstrom, M. Dohlsten, R.-P. Sekaly, and W. Mourad Staphylococcal Enterotoxin D Is a Promiscuous Superantigen Offering Multiple Modes of Interactions With the MHC Class II Receptors J. Immunol., January 1, 1998; 160(1): 225 - 232. [Abstract] [Full Text] [PDF]

				P. M. Lavoie, J. Thibodeau, I. Cloutier, R. Busch, and R.-P. Sekaly Selective binding of bacterial toxins to major histocompatibility complex class II-expressing cells is controlled by invariant chain and HLA-DM PNAS, June 24, 1997; 94(13): 6892 - 6897. [Abstract] [Full Text] [PDF]

				J Kim, R. Urban, J. Strominger, and D. Wiley Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1 Science, December 16, 1994; 266(5192): 1870 - 1874. [Abstract] [PDF]

				J Thibodeau, I Cloutier, P. Lavoie, N Labrecque, W Mourad, T Jardetzky, and R. Sekaly Subsets of HLA-DR1 molecules defined by SEB and TSST-1 binding Science, December 16, 1994; 266(5192): 1874 - 1878. [Abstract] [PDF]