T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A.
We have examined the interaction of the microbial superantigen staphylococcal enterotoxin A (SEA) with peptides corresponding to overlapping regions of the T-cell antigen receptor beta chain variable region V beta 3. SEA is known to stimulate murine T cells bearing certain V beta elements, among them V beta 3. Five peptides were synthesized representing amino acids 1-24, 20-44, 39-60, 57-77, and 74-95 of V beta 3. We demonstrate here that soluble V beta 3-bearing beta chains can bind to a complex of SEA and major histocompatibility complex class II and that the synthetic peptide V beta 3-(57-77) blocked this interaction. The peptide V beta 3-(57-77) also inhibited SEA-induced interferon-gamma production and SEA-induced proliferation of B10.BR spleen cells. Conversely, the peptide corresponding to amino acids 57-77 of V beta 8.2, a V beta element that is not recognized by SEA, decreased staphylococcal enterotoxin C-2-induced proliferation but did not affect SEA-induced proliferation. The peptide inhibition of SEA-induced function was due at least in part to inhibition of V beta 3-bearing T-cell activity, since the percentage of T cells reactive with an anti-V beta 3 monoclonal antibody was significantly reduced by V beta 3-(57-77). These data suggest that the region of V beta 3 encompassing amino acids 57-77 is an area that displays the appropriate sequence and conformation for binding of the SEA molecule and blocking of the resultant interaction with the T-cell antigen receptor.
Pontzer
C H
CH
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611.
Irwin
M J
MJ
Gascoigne
N R
NR
Johnson
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002051:Burkitt Lymphoma; D002460:Cell Line; D010856:Columbidae; D004768:Enterotoxins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D004768:Enterotoxins; D046911:Macromolecular Substances; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C026066:enterotoxin A, Staphylococcal