Inhibition of antigen-specific T cell activation by staphylococcal enterotoxins.
The staphylococcal enterotoxins SEA, SEB, SEC2, and TSST-1 bind to MHC class II molecules and stimulate polyclonal T cell populations on the basis of the expression of responsive TCR V beta domains. CL-1 is a human T cell clone that is specific for a peptide derived from influenza hemagglutinin (HA 307-319) presented in the context of HLA-DR1. CL-1 expresses the TCR V beta 13.1 domain, and does not respond to SEA, SEB, or TSST-1. This T cell was used to test the effect of nonstimulatory staphylococcal enterotoxins on a response to antigenic peptide. These toxins inhibit peptide-specific activation of CL-1 in a concentration-dependent manner. These toxins also inhibit the response of an HLA-DR1-specific alloreactive T cell clone. This inhibition seems to be a result of impaired access of TCR to the MHC/peptide complex rather than negative signaling by toxin via class II interaction or induction of T cell anergy. SEA, but neither SEB nor TSST-1 impedes avidin access to a biotin group attached to the amino terminus of HA 307-319. SEA partially impairs access of avidin to HA peptide biotinylated at residue 313, but is unable to inhibit avidin access to biotin at residue 318. This demonstrates that SEA binds to HLA-DR molecules that have also bound the antigenic peptide and suggests a topology for the interaction of SEA with class II, whereby the toxin interferes with peptide/MHC-TCR contact.
Dowd
J E
JE
Simmons Arthritis Research Center, University of Texas Southwestern Medical Center at Dallas 75235.
Jenkins
R N
RN
Karp
D R
DR
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D001360:Avidin / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D001710:Biotin / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D017635:Clonal Anergy / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013210:Staphylococcus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D004768:Enterotoxins; D015798:HLA-DR1 Antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; D001360:Avidin; C026066:enterotoxin A, Staphylococcal; D001710:Biotin