MHC interaction and T cell recognition of carbohydrates and glycopeptides.
The T cell independence of complex polysaccharide Ag has suggested the possibility that carbohydrates may be incapable of T cell recognition because of a failure to interact with MHC restriction elements and/or a failure of MHC/carbohydrate complexes to interact with and be recognized by Ag-specific TCR. We have used two approaches to obtain information about T cell recognition of carbohydrate. First, we have determined the capacity of a series of oligosaccharides and glycolipids to bind a murine class II MHC molecule, IAd. No significant binding was observed with the 26 compounds tested, but the limitation to these studies was that there was a relatively limited collection of synthetic carbohydrate and glycolipid structures of limited complexity available for analysis. The second approach involved the study of the effect of glycosylation of a known peptide T cell epitope (OVA 323-339) on MHC binding of the peptide and on T cell recognition. Three patterns of effects were observed: 1) no effect on either binding or T cell recognition. This pattern was observed when the carbohydrate was located at residues removed from the core MHC-binding region. When the carbohydrate was located within the core MHC-binding regions, either 2) glycosylation destroyed both MHC binding and T cell recognition; or 3) glycosylation did not ablate MHC binding or T cell recognition. In this latter instance, there was evidence to indicate that the carbohydrate moiety was an important part of the antigenic determinant recognized by T cells.
Ishioka
G Y
GY
Cytel, San Diego, CA 92121.
Lamont
A G
AG
Thomson
D
D
Bulbow
N
N
Gaeta
F C
FC
Sette
A
A
Grey
H M
HM
D000818:Animals; D002241:Carbohydrates / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D006020:Glycopeptides / Q000276:immunology*; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D002241:Carbohydrates; D006020:Glycopeptides; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments