Localization of an immune functional site on staphylococcal enterotoxin A using the synthetic peptide approach.
Using the synthetic peptide approach, we have identified a part of the staphylococcal enterotoxin A (SEA) molecule that is responsible for stimulation of T cell proliferation and induction of the lymphokine IFN-gamma. Peptides were synthesized corresponding to amino acids 1 to 27, SEA(1-27), and 28 to 45, SEA(28-45). Both peptides were tested for direct competition with SEA for blockage of SEA induced proliferation and production of IFN-gamma by T cells. Further, antibodies were produced to the peptides and tested for their ability to bind to SEA and block SEA function. SEA (1-27), but not SEA (28-45), blocked proliferation of human peripheral T cells and induction of IFN-gamma by the T cell line, L12-R4. The inhibitory effects were specific, because SEA (1-27) did not inhibit the induction of T cell proliferation by the mitogen PHA. Consistent with the direct inhibition of function, antibodies to SEA (1-27), but not SEA (28-45), neutralized the mitogenic activity of SEA on human PBL. The data suggest that a functional site on SEA that is responsible for its modulation of T cell function involves the N-terminal 27 amino acids. Residues 1 to 27 of SEA could potentially interact at either the level of the TCR or may block the proposed binding of SEA to class II MHC Ag, based on recent data showing that these molecules are involved in SEA-induced proliferation.
Pontzer
C H
CH
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611.
Russell
J K
JK
Johnson
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000502:physiology; D000942:Antigens, Bacterial / Q000032:analysis / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D004768:Enterotoxins / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology* / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004768:Enterotoxins; D007106:Immune Sera; D010446:Peptide Fragments; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma