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-Vβ 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.