title: A single-amino-acid variant of the H60 CD8 epitope generates specific immunity with diverse TCR recruitment.
abstract: TCR of CD8 T cells recognizes peptides of 8-9 amino acids in length (epitope) complexed with MHC class I. Peptide ligands differing from an epitope by one or two amino acids are thought to modulate the immune response specific to that epitope. H60 is a minor histocompatibility antigen for which the specific CD8 T-cell response dominates during alloresponse after MHC-matched allogeneic transplantation. In the present study, we developed a transgenic mouse (designated H60H Tg) expressing a variant of H60, designated H60H, in which the arginine residue at position 4 of the H60 epitope sequence (LTFNYRNL) is replaced by a histidine residue (LTFHYRNL). Immunization of female C57BL/6 mice with splenocytes from male H60H Tg induced a CD8 T cell primary response and memory response after re-challenge. The response was CD4 help-dependent, demonstrating the potency of H60H as a cellular antigen. The response induced by the H60H cellular antigen was comparable to that induced by H60 in its peak magnitude and overall immune kinetics. H60H challenge recruited broadly diverse TCRs to the specific response, shaping a TCR repertoire different from that of the natural H60 epitope. However, some of the TCRs did overlap between the H60H- and H60-specific CD8 T cells, suggesting that H60H might modulate the H60-specific response. These results may provide a basis for the modulation of the H60-specific CD8 T-cell response.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Su Jeong
authors.initials: SJ
authors.lastname: Ryu
authors.forename: Ji Yeong
authors.initials: JY
authors.lastname: Jeon
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sproule
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D016827:CD8 Antigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C114735:minor H antigen H60