Identification of an Mhc-DPB1 allele involved in susceptibility to experimental autoimmune encephalomyelitis in rhesus macaques.
Experimental autoimmune encephalomyelitis (EAE) is an inducible autoimmune disorder that in rodents is known to be influenced by genetic background, specifically the Mhc class II region. Immunization of a group of outbred rhesus macaques with bovine high homogenate results in induction of the disease in approximately 65% of the animals. No clear association between the Mamu-DR or -DQ subregion of the rhesus macaque MHC (MhcMamu) and susceptibility or resistance to the disease has been documented. In this communication we describe a CD4+ Th cell line, isolated from an animal diagnosed with EAE, which proliferated in response to purified bovine myelin basic protein (MBP), a major constituent of the myelin sheath surrounding nerve cells. More specifically it only recognized a peptide including residues 61-82 of the molecule. Analysis of the T cell receptor (Tcr) usage of this MBP reactive T cell line 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-specific proliferative response was inhibited by a mAb reactive with MHC-DP molecules. Molecular analysis of the Mamu-DP region, in concert with allogeneic antigen presentation studies, demonstrated that the Mamu-DPB1*01 gene product functions as the restriction element for MBP peptide presentation. Retrospective analyses showed that this particular 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*01 allele may represent one of the risk factors involved in determining susceptibility to EAE in an outbred population of rhesus macaques.
Slierendregt
B L
BL
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Hall
M
M
't Hart
B
B
Otting
N
N
Anholts
J
J
Verduin
W
W
Claas
F
F
Jonker
M
M
Lanchbury
J S
JS
Bontrop
R E
RE
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001921:Brain / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle; D004198:Disease Susceptibility / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000737:chemistry; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D008253:Macaca mulatta / Q000276:immunology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014020:Tissue Extracts / Q000276:immunology
D006681:HLA-D Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D014020:Tissue Extracts