Molecular characterization and role in T cell activation of staphylococcal enterotoxin A binding to the HLA-DR alpha-chain.
Superantigens bind to MHC class II-positive cells and stimulate T lymphocytes expressing specific V beta regions of the TCR. Two distinct regions of staphylococcal enterotoxin A superantigen (SEA) have been shown to affect the binding to MHC class II molecules. Results presented here demonstrate for the first time that the SEA-DR interaction can be affected by mutations on the class II alpha-chain. Furthermore, we have precisely mapped the interaction of the SEA N-terminal domain with the alpha1 domain of HLA-DR. Scatchard analysis using DAP cells transfected with mutant class II molecules showed a role for residue DR alpha K39 in the binding of SEA. Also, complementation experiments using mutant SEA molecules revealed an interaction between SEA residue F47 and position alphaQ18 on an outer loop of HLA-DR. These interactions between SEAF47 and the DR alpha-chain are critical, as they allow the recognition by an otherwise nonreactive V beta1+ T cell hybridoma and induction of tyrosine phosphorylation through the TCR.
Thibodeau
J
J
Laboratory of Immunology, Institute of Clinical Research of Montreal, Quebec, Canada.
Dohlsten
M
M
Cloutier
I
I
Lavoie
P M
PM
Bjork
P
P
Michel
F
F
Léveillé
C
C
Mourad
W
W
Kalland
T
T
Sékaly
R P
RP
D000818:Animals; D002460:Cell Line; D004768:Enterotoxins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D004768:Enterotoxins; D006684:HLA-DR Antigens; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal