Fine specificity of peptide determinants for indirect T cell recognition of class I MHC alloantigens

CD4+ T cells from the LEW (RT1l) rat strain are able to recognize a 24-amino acid peptide from the alpha-helical region of the alpha 1-domain of the DA (RT1avl) RT1.A class I MHC molecule. This response is known to play a role in the effector mechanisms of rejection of DA grafts by LEW recipients. In this study, we demonstrate that the WAG (RT1u) strain is also able to respond to this peptide, but that the PVG (RT1c) strain does not respond. Fine specificity studies using a nested set of 15 mers derived from the 24 mer indicate that the LEW strain recognizes multiple T cell epitopes spanning the length of the peptide, while the WAG strain response is limited to the N-terminal region. With regard to B cell immunity, both the LEW and WAG strains give strong antibody responses when immunized with the free peptide, while the antibody response in the PVG strain is weak. Interestingly, in all 3 strains, the antibodies appear to be directed at the N- and C-terminal regions of the peptide, and to be almost entirely dependent upon the presence of the N- and C-terminal amino acids. These studies are potentially important when considering the specificity of rejection responses, and most particularly when considering the specific suppression of rejection mediated by indirect T cell allorecognition.