Efficient presentation of myelin oligodendrocyte glycoprotein peptides but not protein by astrocytes from HLA-DR2 and HLA-DR4 transgenic mice.
The role of astrocytes in the pathogenesis of multiple sclerosis (MS) is not well understood. Astrocytes may modulate the activity of pathogenic T cells by presenting myelin antigens in combination with pro- or anti-inflammatory signals. Astrocytes have been shown to present myelin basic protein (MBP) and proteolipid protein (PLP) to T cells, but it has remained unresolved whether astrocytes present myelin oligodendrocyte glycoprotein (MOG), which has been implicated as an important autoantigen in MS. Here, we asked whether astrocytes presented MOG to T cells. To closer model presentation of human MOG by astrocytes in MS patients, we generated astrocytes from transgenic mice expressing the MS-associated MHC class II alleles HLA-DR2 (DRB1*1501) and HLA-DR4 (DRB1*0401). The results show that IFN-gamma-activated HLA-DR2 and HLA-DR4 expressing astrocytes efficiently presented immunodominant and subdominant MOG peptides to T cells. The hierarchy of the presented MOG epitopes was comparable to that of professional APCs, including dendritic cells and microglia. Importantly, astrocytes were poor at processing and presenting native MOG protein. Furthermore, astrocytes induced a mixed Th1/Th2 cytokine response in MOG-specific T cells, whereas dendritic cells induced a predominantly Th1 cell response. Collectively, the results suggest that astrocytes may modulate anti-MOG T cell responses in the CNS.
Kort
Jens J
JJ
Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, USA.
Kawamura
Kazuyuki
K
Fugger
Lars
L
Weissert
Robert
R
Forsthuber
Thomas G
TG
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D001253:Astrocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015802:HLA-DR2 Antigen / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015802:HLA-DR2 Antigen; D015804:HLA-DR4 Antigen; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments