title: HLA-DR-restricted presentation of purified myelin basic protein is independent of intracellular processing.
abstract: 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.
authors.affiliation: Neuroimmunology Branch, NINDS, NIH, Bethesda, MD 20892-1400, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vergelli
authors.forename: V
authors.initials: V
authors.lastname: Pinet
authors.forename: A B
authors.initials: AB
authors.lastname: Vogt
authors.forename: M
authors.initials: M
authors.lastname: Kalbus
authors.forename: M
authors.initials: M
authors.lastname: Malnati
authors.forename: P
authors.initials: P
authors.lastname: Riccio
authors.forename: E O
authors.initials: EO
authors.lastname: Long
authors.forename: R
authors.initials: R
authors.lastname: Martin
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002999:Clone Cells; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015798:HLA-DR1 Antigen / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D050356:Lipid Metabolism; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D015853:Cysteine Proteinase Inhibitors; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; C045084:invariant chain; D007930:Leucine; C024974:E 64