We generated transgenic mice that expressed hen egg-white lysozyme (HEL) under a class II MHC promoter. The A7 line expressed HEL with a point mutation in the Asp52 residue, the main anchor amino acid responsible for the selection of the chemically dominant family of peptides (52-60) by I-Ak molecules. Mice expressing HEL with Ala52 were completely unresponsive when immunized with the same protein, i.e., HEL A52. However, the same mice immunized with wild-type HEL elicited T cells that recognized a conformation of the 52-61 core sequence uniquely different between Asp52 and Ala52 containing peptides. Importantly, some T cells also recognized the HEL A52 peptide given exogenously but not the same peptide processed from HEL A52 protein. Thus, a core MHC anchor residue influences markedly the specificity of the T cells. We discuss the relevance of these findings to autoimmunity and vaccination with altered peptides.
ASJC Scopus subject areas
- Immunology and Allergy