Résumé
Antigen presentation to CD4+ T cells involves intracellular antigen processing and loading of peptides onto newly synthesized major histocompatibility complex (MHC)‐class II molecules. Some antigens, such as the lipid‐bound, native form of myelin basic protein (LB‐MBP) can also be presented by recycling of cell surface MHC class II molecules. The data reported here demonstrate that a preparation of highly purified, delipidated MBP (HP‐MBP) follows yet another presentation pathway. Similar to LB‐MBP, presentation of HP‐MBP to HLA‐DR1‐restricted T cells was independent of HLA‐DM, of newly synthesized proteins, and of invariant chain expression. However, in contrast to LB‐MBP, presentation of HP‐MBP was also independent of internalization of surface HLA‐DR molecules. The different requirements for the presentation of the two molecular forms of MBP were further confirmed by use of the protease inhibitor E64: presentation of LB‐MBP but not of HP‐MBP was inhibited after treatment of target cells with E64. Furthermore, intact HP‐MPB bound to isolated HLA‐DR molecules in vitro with an association rate that was considerably faster than that of short peptides. These results show that presentation of HP‐MBP is independent of intracellular processing and suggest that it may be presented to T cells by direct binding to surface HLA‐DR molecules.