Predictions of T-cell receptor- and major histocompatibility complex-binding sites on staphylococcal enterotoxin C1.
We have focused on regions of staphylococcal enterotoxin C1 (SEC1) causing immunomodulation. N-terminal deletion mutants lacking residues 6 through 13 induced T-cell proliferation similar to that induced by native toxin. However, mutants with residues deleted between positions 19 and 33, although nonmitogenic themselves, were able to inhibit both SEC1-induced T-cell proliferation and binding of the native toxin to major histocompatibility complex (MHC) class II. Presumably, these deletions define a part of SEC1 that interacts with the T-cell receptor. Three synthetic peptides containing residues located in a region analogous to the alpha 5 groove of SEC3 had residual mitogenic activity or blocked T-cell proliferation induced by SEC1 and appear to recognize the same site as SEC1 on a receptor for the toxin, presumably MHC class II. We conclude that isolated portions of the SEC1 molecule can retain residual mitogenic activity but that the entire protein is needed to achieve maximal superantigenic stimulation. Our results, together with the results of other investigators, support a model in which SEC1 binds to an alpha helix of MHC class II through a central groove in the toxin and thereby promotes or stabilizes the interaction between antigen-presenting cells and T cells.
Hoffmann
M L
ML
Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow 83843.
Jablonski
L M
LM
Crum
K K
KK
Hackett
S P
SP
Chi
Y I
YI
Stauffacher
C V
CV
Stevens
D L
DL
Bohach
G A
GA
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000472:pathogenicity*
D016207:Cytokines; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C034959:enterotoxin C, staphylococcal