Analysis of the interaction site for the self superantigen Mls-1a on T cell receptor V beta.
Superantigen bound to major histocompatibility complex (MHC) products have been shown to stimulate T cells in a V beta-specific manner. Mouse T cells bearing V beta 8.1 usually respond to the self superantigen, Mls-1a, whereas T cells bearing V beta 8.2a do not. Previously, using site-directed mutational analysis, we identified the residues of natural variants of T cell receptor (TCR) V beta 8.2 that conferred Mls-1a reactivity. These residues are predicted to lie on a beta-pleated sheet of the TCR V beta element, well away from the expected binding site for antigen and MHC proteins. This study was undertaken to determine the effect of glycosylation on this beta-pleated sheet on Mls-1a reactivity and to map the extent of the interaction site on V beta 8.2 for Mls-1a. to Mls-1a, as well as to peptides derived from the conventional protein antigen, chicken ovalbumin. Here we demonstrate that first, N-linked carbohydrate on the lateral surface of V beta blocks the interaction of the TCR V beta with the self superantigen, Mls-1a, but has no effect on the TCR interaction with peptide antigen and MHC, second, that the interaction site for Mls-1a extends over the surface of the solvent-exposed beta-pleated sheet on the side of the TCR, and third, that mutations which affect both superantigen and peptide antigen reactivity lie at the beginning of the first complementarity determining region of V beta, consistent with models of the trimolecular complex of TCR-peptide-MHC.
Pullen
A M
AM
Howard Hughes Medical Institute, Denver, Colorado.
Bill
J
J
Kubo
R T
RT
Marrack
P
P
Kappler
J W
JW
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D002241:Carbohydrates / Q000494:pharmacology; D002460:Cell Line; D006031:Glycosylation; D007135:Immunoglobulin Variable Region / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D016747:Minor Lymphocyte Stimulatory Antigens; D009154:Mutation / Q000235:genetics; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology / Q000648:ultrastructure
D000954:Antigens, Surface; D002241:Carbohydrates; D007135:Immunoglobulin Variable Region; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell