Unusually diverse T cell response to a repeating tripeptide epitope.
The immune system utilizes a diverse T cell repertoire for the recognition of foreign antigens in the context of self MHC gene products. We have examined the potential diversity of the T cell response directed to a immunodominant repeating tripeptide epitope (EYA)5. This peptide represents one of the two T cell epitopes on the synthetic alpha-helical polypeptide antigen Poly 18, Poly EYK(EYA)5 in H-2d mice and does not require antigen processing prior to presentation to Poly 18-specific T cell hybridomas. The T cell response directed to the repeating tripeptide epitope (EYA)5 is extremely heterogenous even though the epitope has a relatively simple amino acid sequence. We have analyzed the fine specificity of 21 randomly chosen Poly 18-reactive, (EYA)5-specific and H-2d-restricted T cell hybridomas derived from H-2d, H-2bxd, and H-2b----H-2bxd Poly 18-responding mice to determine the number of unique antigen reactivity patterns represented by this T cell population. We used alanine- and/or lysine-substituted (EYA)5 peptides and a panel of haplotype-varied splenocytes and observed a great deal of microheterogeneity in response. We find that 13 of the 21 hybridomas have a distinct fine antigen specificity and T cell receptors. The binding of (EYA)5 to the antigen-binding groove of I-Ad appears to generate a highly diversified T cell response. Therefore, (EYA)5-I-Ad complex allows the activation of unrelated T cell clonotypes with the same overall antigen specificity and MHC restriction, but with distinct microheterogeneity in response and receptor usage.
Novak
Z
Z
Department of Immunology, University of Alberta, Edmonton, Canada.
Boyer
M
M
Kilgannon
P
P
Fraga
E
E
Fotedar
A
A
Singh
B
B
D000409:Alanine; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001853:Bone Marrow / Q000528:radiation effects; D002678:Chimera; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D007376:Interleukin-2 / Q000032:analysis; D016131:Lymphocyte Subsets / Q000276:immunology*; D008239:Lysine; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D010455:Peptides; D008239:Lysine; D000409:Alanine