A biological function for the XP motif within the N terminus of major histocompatibility complex class II-associated peptides.
A high proportion (up to 30%) of major histocompatibility complex (MHC) class II-bound peptides in the mouse and humans contains a proline residue at the N-terminal penultimate position (XP motif). We used a set of ovalbumin (OVA)-specific and hen egg lysozyme (HEL)-specific T cell hybridomas and asked whether the XP motif in MHC class II-associated peptides might influence the stimulation of T cells. We created N-terminally substituted variants of OVA323-339, an H2-Ad restricted OVA epitope and of HEL50-63, a dominant epitope in the context of H2-Ak. 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.
Breloer
M
M
Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany.
Ehrlich
S
S
Fleischer
B
B
von Bonin
A
A
D000595:Amino Acid Sequence / Q000502:physiology*; D000818:Animals; D000939:Epitopes / Q000276:immunology; D006207:Half-Life; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000502:physiology*; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000502:physiology*; D011392:Proline / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D010047:Ovalbumin; D011392:Proline