Determination of amino acids on agretopes of pigeon cytochrome c-related peptides specifically bound to I-A allelic products.
In our prior study it was demonstrated that residues 46 and 54 on a synthetic peptide, AEGFSYTVANKNKGIT (50V), work as an agretope (site contacts with major histocompatibility complex molecules) and residues 50 and 52 function as an epitope (site contacts with T cell receptor), when tri-molecular complexes are formed among 50V,I-Ab and the T cell receptor. 50V was composed of residues 43 to 58 of pigeon cytochrome c (p43-58) except that the aspartic acid (D) at residue 50 was substituted by valine (V). Substitution of agretopic residues on 50V changed this I-Ab-binding peptide to an I-Ak-binding peptide, suggesting that positions 46 and 54 work as an agretope in I-Ak-restricted T cell responses. In the present study we examined whether residues 46 and 54 of 50V worked as agretopes in T cell responses restricted to other I-A haplotypes. The 50V-related peptides with phenylalanine (F) at position 46 and alanine (A) at position 54 bound tightly to I-Ab, I-Ad, I-Aq and I-As molecules and stimulated T cells most potently in mice bearing these I-A haplotypes. In contrast, 50V-related peptides carrying D at position 46 and A at position 54 bound most potently to I-Ak molecules, and the peptides with arginine (R) at position 46 and A at position 54 bound most efficiently to I-Av molecules. The present findings, thus, demonstrate that the agretopic positions on the p43-58 related peptides are preserved in T cell responses restricted to each I-A haplotype studied, and that the specific amino acids on the agretopic positions exist a priori for each I-A allele-specific structure.
Itoh
Y
Y
Section of Pathology, Hokkaido University, Sapporo, Japan.
Ogasawara
K
K
Takami
K
K
Gotohda
T
T
Naruse
H
H
Good
R A
RA
Onoé
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D010856:Columbidae; D003574:Cytochrome c Group / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes
D003574:Cytochrome c Group; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments