Alloreactive 2C T cells recognize a self peptide in the context of the mutant Kbm3 molecule.
Previous studies hav shown that 2C T cells have dual specificity for Ld and Kbm3 alloantigens and are positively selected in the context of Kb. Analysis of Kbm3-eluted peptides reveals a single HPLC fraction that is a central component of the Kbm3 allodeterminant. Peptides with biologic and biochemical properties indistinguishable from those of the Kbm3 allopeptide were also isolated from Kb and Kbm8, despite the fact that cells bearing these class I molecules are not efficient targets for 2C T cells. The allopeptide was isolated and compared with p2Ca, the Ld allopeptide recognized by 2C T cells in the context of Ld. The Kbm3 allopeptide was found to be biochemically and functionally different from p2Ca. Therefore, the 2C TCR has dual specificity for two different peptides presented in the context of two structurally distinct class I molecules. The possibility of a common peptide being bound by Kb, Kbm3, and Kbm8 suggests that the peptide defined as an allodeterminant in the context of Kbm3 may also function in the positive selection of 2C T cells when presented in the context of Kb and Kbm8 during thymic development. In support of this view, the allopeptide was also found in Kb and Kbm8 thymic peptide eluates.
Tallquist
M D
MD
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Pease
L R
LR
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D007519:Isoantigens / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000276:immunology; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000737:chemistry
D001324:Autoantigens; D000939:Epitopes; D006183:H-2 Antigens; D007519:Isoantigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell