Differing MHC class I requirements for induction and propagation of experimental systemic lupus erythematosus.
Mice deficient in beta2-microglobulin expression are resistant to the induction of experimental systemic lupus erythematosus (SLE). The present studies were designed to identify the beta2-microglobulin-dependent cell surface molecule(s) that confers sensitivity to experimental SLE, and to determine its role in disease development. We report hat mice lacking the transporter associated with antigen presentation (TAP-/-) were also resistant to disease, whereas CD1-/- and CD8-/- mice were susceptible; susceptibility also did not correlate with neonatal Fc receptor or HEPH expression. These data indicate that disease susceptibility is determined by expression of MHC class I. Furthermore, by analyzing both adoptive transfer and radiation bone marrow chimeras, we demonstrate that MHC class I expression is necessary for propagation of disease, but not for induction of pathogenic cells.
Singer
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DS
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Dinah.Singer@nih.gov
Zinger
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Kohn
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Mozes
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D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D018949:Antigens, CD1; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin