IDENTIFICATION OF AN MHC-DPB1 ALLELE INVOLVED IN SUSCEPTIBILITY TO EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN RHESUS MACAQUES

Experimental autoimmune encephalomyelitis (EAE) is an inducible autoim mune disorder that in rodents is known to be influenced by genetic bac kground, specifically the Mhc class II region. Immunization of a group of outbred rhesus macaques with bovine brain homogenate results in in duction of the disease in similar to 65% of the animals. No clear asso ciation between the Mamu-DR or -DQ subregion of the rhesus macaque MHC (MhcMamu) and susceptibility or resistance to the disease has been do cumented. In this communication we describe a CD4(+) T-h cell line, is olated from an animal diagnosed with EAE, which proliferated in respon se to purified bovine myelin basic protein (MBP), a major constituent of the myelin sheath surrounding nerve cells. More specifically it onl y recognized a peptide including residues 61-82 of the molecule. Analy sis of the T cell receptor (Tcr) usage of this MBP reactive T cell lin e showed functional transcripts for only two members of the V(alpha)1 and one of each of the V(beta)3 and V(beta)6 families. The antigen-spe cific proliferative response was inhibited by a mAb reactive with MHC- DP molecules. Molecular analysis of the Mamu-DP region, in concert wit h allogeneic antigen presentation studies, demonstrated that the Mamu- DPB1 star 01 gene product functions as the restriction element for MBP peptide presentation. Retrospective analyses showed that this particu lar allele is frequently found in the group of EAE susceptible animals but is absent in the resistant animals (P < 0.01). As a consequence, the Mamu-DPB1 star 01 allele may represent one of the risk factors inv olved in determining susceptibility to EAE in an outbred population of rhesus macaques.