Binding of toxic shock syndrome toxin-1 to murine major histocompatibility complex class II molecules.
The staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) has potent stimulatory effects on murine and human lymphocytes. This is the consequence of TSST-1 binding to major histocompatibility complex (MHC) class II molecules and the engagement in a V beta-restricted fashion of the T cell receptor by the TSST-1-MHC class II complex. Using radioligand and functional assays we have recently shown that TSST-1 binds to all HLA-DR (n = 14), HLA-DQ (n = 2) and HLA-DP (n = 2) phenotypes tested. In this study, we have examined the ability of murine MHC class II molecules to bind TSST-1. Specific high-affinity binding of TSST-1 was detectable to unfractionated BALB-c (H-2d) and C57BL/6 (H-2b), but not to C3H (H-2k) spleen cells. The Kd of this binding estimated from Scatchard analysis was in the same nanomolar range as the Kd of binding of TSST-1 to HLA-DR. Binding of 125I-labeled TSST-1 to BALB/c-derived B cell lymphoma lines and to L cell transfectants correlated with the expression of I-A molecules, but not with the expression of I-E molecules. Furthermore, I-A+, I-E- cells but not I-A-, I-E+ cells were able to support TSST-1-induced T cell proliferation. The binding affinity of TSST-1 for I-Ak appears to be much lower than for I-Ad. L cell transfectants expressing hybrid DR alpha: I-E beta k molecules, but not those expressing I-E alpha k: DR1 beta molecules, could bind TSST-1 and efficiently support TSST-1-induced T cell proliferation. This suggests that minor differences in the highly homologous I-E alpha and DR alpha chains are critical in determining the affinity of the MHC class II molecule for TSST-1. These results demonstrate that the binding of TSST-1 to MHC class II molecules in the mouse, in contrast to humans, is strongly influenced by phenotype. Analysis of the molecular basis of these differences may help to localize staphylococcal exotoxin binding sites on MHC class II molecules.
Division of Allergy and Immunology, Children's Hospital, Boston, MA 02115.
P R
PR
Scholl
R P
RP
Sekaly
A
A
Diez
L H
LH
Glimcher
R S
RS
Geha
D000818:Animals; D001427:Bacterial Toxins; D001665:Binding Sites; D004768:Enterotoxins / Q000378:metabolism* / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000378:metabolism; D018089:Superantigens
D001427:Bacterial Toxins; D004768:Enterotoxins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal