A BIOLOGICAL FUNCTION FOR THE XP MOTIF WITHIN THE N-TERMINUS OF MAJORHISTOCOMPATIBILITY COMPLEX CLASS II-ASSOCIATED PEPTIDES

A high proportion (up to 30 %) of major histocompatibility complex (MH C) class II-bound peptides in the mouse and humans contains a proline residue at the N-terminal penultimate position (XP motif). We used a s et of ovalbumin (OVA)-specific and hen egg lysozyme (HEL)-specific T c ell hybridomas and asked whether the XP motif in MHC class II-associat ed peptides might influence the stimulation of T cells. We created N-t erminally substituted variants of OVA323-339, an H2-A(d) restricted OV A epitope and of HEL50-63, a dominant epitope in the context of H2-A(k ). Our results show that the N-terminal sequence of MHC class II-bound peptides has a strong impact for the overall stimulation of specific T cells. Proline at the N terminus of antigenic peptides, in contrast to other amino acids, is tolerated or even enhances the recognition of MHC class II-bound peptides significantly.