title: Presentation of alpha B-crystallin to T cells in active multiple sclerosis lesions: an early event following inflammatory demyelination.
abstract: In the development of multiple sclerosis (MS), (re)activation of infiltrating T cells by myelin-derived Ags is considered to be a crucial step. Previously, alpha B-crystallin has been shown to be an important myelin Ag to human T cells. Since alpha B-crystallin is an intracellular heat shock protein, the question arises at what stage, if any, during lesional development in MS this Ag becomes available for CD4+ T cells. In 3 of 10 active MS lesions, alpha B-crystallin could be detected inside phagocytic vesicles of perivascular macrophages, colocalizing with myelin basic protein and myelin oligodendrocyte glycoprotein (MOG). Although the detectability of MOG in phagosomes is considered as a marker for very recent demyelination, MOG was detected in more macrophages and in more lesions than alpha B-crystallin. The disappearance of alpha B-crystallin from macrophages even before MOG was confirmed by in vitro studies; within 6 h after myelin-uptake alpha B-crystallin disappears from the phagosomes. Alpha B-crystallin-containing macrophages colocalized with infiltrating T cells and they were characterized by expression of MHC class II, CD40, and CD80. To examine functional presentation of myelin Ags to T cells, purified macrophages were pulsed in vitro with whole myelin membranes. These macrophages activated both myelin-primed and alpha B-crystallin-primed T cells in terms of proliferation and IFN-gamma secretion. In addition, alpha B-crystallin-pulsed macrophages activated myelin-primed T cells to the same extent as myelin-pulsed macrophages, whereas myelin basic protein-pulsed macrophages triggered no response at all. These data indicate that, in active MS lesions, alpha B-crystallin is available for functional presentation to T cells early during inflammatory demyelination.
authors.affiliation: Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Bajramović
authors.forename: A C
authors.initials: AC
authors.lastname: Plomp
authors.forename: A v
authors.initials: Av
authors.lastname: Goes
authors.forename: C
authors.initials: C
authors.lastname: Koevoets
authors.forename: J
authors.initials: J
authors.lastname: Newcombe
authors.forename: M L
authors.initials: ML
authors.lastname: Cuzner
authors.forename: J M
authors.initials: JM
authors.lastname: van Noort
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D003459:Crystallins / Q000276:immunology* / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D001324:Autoantigens; D018122:B7-1 Antigen; D019013:CD40 Antigens; D003459:Crystallins; D000949:Histocompatibility Antigens Class II; D009185:Myelin Proteins; D002403:Cathepsins