The existence of two completely distinct antigenic sites within a decapeptide.
A decapeptide (1182-1191) derived from the bovine interphotoreceptor retinoid-binding protein (IRBP) was found to contain two completely distinct antigenic sites when tested in Lewis rats. One site, localized in sequence 1182-1191, is the core of the immunodominant and highly uveitogenic determinant of IRBP. The second site localizes within sequence 1183-1191 and becomes detectable only when tryptophan at position 1182 is deleted. Lymphocytes sensitized against the first, larger site recognized all longer peptides within sequence 1169-1191, as well as whole IRBP. In contrast, lymphocytes sensitized against the second, short epitope recognized only two peptides, 1184-1191 and (to a lesser degree) 1183-1191. The responses to both sites were restricted by the same major histocompatibility complex (MHC) product (I-A), as shown by monoclonal antibody blocking and by the finding that the lymphocyte response to 1184-1191 was competitively inhibited by peptide 1181-1191. The unique finding of two completely distinct antigenic sites within a decapeptide could be explained by the hypothesis that peptides of the two sites combine with the MHC molecule on antigen-presenting cells by different configurations, thus forming two distinct antigenicities.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
S
S
Kotake
Y
Y
Sasamoto
Y
Y
Kawano
H
H
Sanui
B
B
Wiggert
G J
GJ
Chader
I
I
Gery
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001666:Binding Sites, Antibody / Q000032:analysis*; D002455:Cell Division; D000939:Epitopes / Q000032:analysis*; D005136:Eye Proteins; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000032:analysis* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014364:Tryptophan; D000099214:Retinol-Binding Proteins, Interstitial
D000911:Antibodies, Monoclonal; D000939:Epitopes; D005136:Eye Proteins; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D012177:Retinol-Binding Proteins; D014364:Tryptophan; D000099214:Retinol-Binding Proteins, Interstitial