Peptide affinity for MHC influences the phenotype of CD8(+) T cells primed in vivo.
Priming C57BL/6 mice with dominant antigenic peptides of ovalbumin (OVA) or bovine insulin (INS) in complete Freund's adjuvant generates antigen-specific, H-2K(b)-restricted, CD8(+) CTL. OVA-CTL produced type 1 cytokines IFN-gamma and TNF-alpha, whereas INS-CTL produced IL-5 and IL-10 with low levels of IL-4 and IFN-gamma. Here, we investigate whether differential binding affinities of the OVA and INS peptides to H-2K(b) influence the phenotype of the CD8(+) CTL. OVA(257-264) was found to have significantly higher binding affinity than the INS A-chain(12-21) toward K(b). Exchanging the MHC anchor residues between the OVA and INS peptides reversed the K(b) binding capacity of the altered peptides. The lower affinity, altered OVA peptides induced CTL that produced IL-5 and IL-10 in addition to IFN-gamma, whereas high binding affinity, altered INS peptides induced CTL that produced IFN-gamma but not IL-5 or IL-10. These data suggest that MHC binding affinity of peptides can regulate the phenotype of the resulting CD8(+) T cells.
Ma
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Department of Ophthalmology, Winship Cancer Institute, Atlanta, Georgia 30322, USA.
Kapp
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D004527:Egg Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D006183:H-2 Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004527:Egg Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; C452719:INS A(12-21); D016056:Immunodominant Epitopes; D007328:Insulin; C110366:OVA-8; D010446:Peptide Fragments; D010455:Peptides; D010047:Ovalbumin