T cell recognition of Tn-glycosylated peptide antigens.
The mouse hemoglobin-derived decapeptide Hb (67-76), VITAFNEGLK, which binds well to Ek and is non-immunogenic in CBA/J mice, was O-glycosylated with the tumor-associated carbohydrate Tn (alpha-D-N-acetylgalactosamine, or alpha-D-GalNAc). Each of the ten positions in the peptide was substituted with serine or threonine having the Tn antigen attached. The complete set of Tn-glycosylated peptides were then studied for binding to Ek and for immunogenicity in CBA/J mice. All of those glycopeptides which had the Tn attached to serine or threonine at a position in the peptide where, according to the crystal structure determinations, the amino acid side chain was oriented downwards into the binding site of the major histocompatibility complex (MHC) molecule, completely lost their capacity for binding to Ek. This was the case for the glycopeptides with Tn attached at position 68 and 76, which are the major anchor residues and for those with Tn attached at position 71 and 73, which function as secondary anchor residues. Those glycopeptides which had Tn attached to serine or threonine at positions where the side chain pointed away from the binding site maintained their capacity for binding to Ek, except for those with Tn attached at position 70 and 74. Furthermore, some of the MHC-binding glycopeptides were immunogenic. In particular, this was the case for the glycopeptide with Tn attached to the central position 72 in the decapeptide. From previous studies, this is known to be the dominant T cell receptor contact residue of Hb (67-76). The results suggest that T cells may be capable of recognizing epitopes which are partially defined by a small glycan group.
Jensen
T
T
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark. T.Jensen@immi.ku.dk
Galli-Stampino
L
L
Mouritsen
S
S
Frische
K
K
Peters
S
S
Meldal
M
M
Werdelin
O
O
D000595:Amino Acid Sequence; D000818:Animals; D003429:Cross Reactions; D005260:Female; D005914:Globins / Q000737:chemistry / Q000276:immunology; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D006020:Glycopeptides; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D005914:Globins