[Detection of amino acids on the agretopes of pigeon cytochrome c derived peptide p43-58 specifically bound to mouse MHC class II allelic products].
In our previous study it has been demonstrated that residues 46 and 54 on a pigeon cytochrome c derived peptide, 50V (AEGFSYTVANKNKGIT), work as agretopes (sites contact with MHC molecule) and residues 50 and 52 function as dominant epitopes (sites contact with TCR), when tri-molecular complexes are formed among 50V, I-Ab molecule and TCR. 50V was substituted from aspartic acid to valine at position 50 of p43-58 that was derived from residues 43 to 58 of pigeon cytochrome c. Substitution of agretopic residues on 50V altered this I-Ab binding peptide to an I-Ak binding peptide, suggesting that positions 46 and 54 also worked as agretopes in I-Ak restricted T cell responses. In the present report I examined whether residues 46 and 54 of the p43-58 related peptides worked as agretopes in binding to products of other I-A haplotypes and tried to determine which amino acids on agretopes bound strongly with each I-A molecule. The p43-58 related peptides with phenylalanine(F) at position 46 and alanine(A) at position 54 bound tightly to I-Ab, I-Aq and I-A(s) molecules and stimulated T cells most potently in mice bearing these I-A products. In contrast, p43-58 related peptides carrying aspartic acid(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. These findings demonstrate that the agretopic positions on p43 -58 related peptides are preserved in T cell responses restricted to each I-A haplotype studied, but the specific amino acids on the agretopes exist a priori for each I-A allele specific structure.
Itoh
Y
Y
Section of Pathology, Hokkaido University, Sapporo, Japan.
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D010856:Columbidae; D003574:Cytochrome c Group / Q000737:chemistry*; D000939:Epitopes; D005802:Genes, MHC Class II; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins
D003574:Cytochrome c Group; D000939:Epitopes; D010455:Peptides; D011506:Proteins