Effect of the bm12 class II mutation on proliferative and cytokine responses of encephalitogenic T cells in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis.
The bm12 mutation in the class II I-A(b)molecule can profoundly influence experimental autoimmune disease, enhancing the development of systemic lupus erythematosus-like syndromes in NZB.H-2(bm12)mice or, conversely, abolishing the susceptibility of C57BL/6J (H-2(b)) mice to the induction of experimental autoimmune myasthenia gravis. We have studied the effect of this mutation on experimental autoimmune encephalomyelitis (EAE), induced in H-2(b)mice by myelin oligodendrocyte glycoprotein (MOG), and recently showed that MOG 35-55 peptide (pMOG 35-55), which represents the immunodominant encephalitogenic region for H-2(b)mice, is also a strong encephalitogen for H-2(bm12)mice. Nevertheless, although the differences in fine epitope specificity and TCR-Vbeta gene usage between encephalitogenic pMOG 35-55-specific T cells from H-2(b)and H-2(bm12)mice were subtle, H-2(bm12)and H-2(b)antigen presenting cells failed to effectively cross-present pMOG 35-55 non-syngeneically to I-A(b)/pMOG 33-55- and I-A(bm12)/pMOG 35-55-specific T cells, respectively. In the present study, we show that the abrogation of the response to pMOG 35-55 by the Th1 encephalitogenic pMOG 35-55-specific T cells upon non-syngeneic cross-presentation is neither due to a cytokine shift to a Th2 pattern, nor a result of anergy induction. Therefore, we suggest that presentation of pMOG 35-55 to I-A(b)/pMOG 35-55-specific T cells via the bm12 class II MHC molecule resulted in ineffective stimulation, similar to a weak agonistic effect.
Gur
H
H
Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100, Israel. hanang@post.tau.ac.il
Mendel
I
I
Kerlero de Rosbo
N
N
Ben-Nun
A
A
D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D016056:Immunodominant Epitopes; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments