Role of a C-terminal residue of an immunodominant epitope in T cell activation and repertoire diversity.
In the present study, the extent of heterogeneity in the high responder T cell response to the predominant epitope region of hen egg white lysozyme (HEL46-61) was examined. Through analyses of T cell proliferation and precursor frequency, the C3H T cell response is shown not to be limited to peptides containing the previously defined minimal epitope of residues 52-61, but rather is quite heterogeneous, encompassing much of the 46-61 sequence. Further characterization using a panel of T cell hybridoma clones revealed T cell recognition of diverse minimal epitopes within this region. Interestingly, these T hybridomas could be grouped into three distinct categories based on the ability to respond to peptides with or without the native arginine residue at position 61 (61-required, 61-inhibitory, dual responders). Using analogue peptides containing single amino acid substitutions at position 61, further heterogeneity within these hybridoma groups was identified, suggesting the presence of an extremely diverse T cell repertoire for the epitope region. The charge and/or size of the C-terminal residue appears to be a critical factor for certain clones; replacement of the native arginine residue with aspartic acid or glutamic acid enabled a nonstimulatory ligand to specifically antagonize a T cell hybridoma response. Collectively, these results strongly suggest that the C-terminal residue of the predominant epitope in high responder mice plays a critical role in T cell diversity and activation.
Mikszta
J A
JA
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Jang
Y S
YS
Kim
B S
BS
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D006825:Hybridomas; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology / Q000494:pharmacology; D010455:Peptides / Q000032:analysis / Q000276:immunology / Q000494:pharmacology; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*
D016056:Immunodominant Epitopes; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D009113:Muramidase