Comparison of class I- and II-restricted T cell recognition of the identical peptide.

There is structural and functional evidence that both class I- and II-restricted T cells recognize short processed peptides bound to MHC molecules. Although the structural conformation of bound peptides remains unknown, no evidence of distinct structural motifs of class I- or class II-restricted peptides has been described. Conversely, two algorithms proposed to predict T cell epitopes, and based on primary amino acid sequence or tertiary structure, are both compatible with many observed class I- and class II-restricted peptides. We previously identified eight class I-restricted peptides which were also recognized by class II-restricted T cells. Based on functional and direct binding studies, additional examples of peptides with both class I and II restrictions have been identified. In this study, we have directly compared the fine specificity of T cell recognition of a single epitope in a single mouse strain in the context of both class I- and class II-restricted responses. Based on a panel of analogue peptides with amino acid substitutions and peptides of various lengths, we observed several striking similarities in the recognition patterns of both class I- and class II-restricted T cells. In addition, some characteristics of recognition were different in the two systems indicating that the recognition processes were similar but not identical.