HLA, molecular mimicry and multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system in which an autoimmune response most probably contributes to pathogenesis. To date, the best characterized susceptibility-associated gene has been mapped to the HLA complex. The HLA-DRB1*1501 - DRB5*0101 - DQA1*0102 - DQB1*0602 haplotype is both associated and linked to MS in different ethnic groups. The locus within the HLA class II region encoding the MS-susceptibility gene is under intensive investigation. Epidemiological studies, however, have suggested that environmental antigens also play a critical role in MS pathogenesis. One of the ways a pathogen could trigger autoimmune disease is via immunological cross-reactivity or molecular mimicry. This concept argues that a microbial peptide with certain degree of homology to a self peptide can stimulate pathogenic self-reactive specific T cells to cause an autoimmune disease. Many microbial agents have regions of sequences that may serve as binding motifs for HLA-DR2. HLA genetics and molecular mimicry may therefore be intimately interlinked in the disease process. In the present review, we focus on the HLA association with MS and the role of microbial antigens in MS, with special reference to the molecular mimicry hypothesis.
Liblau
R
R
Institut National de la Santé et de la Recherche Médicale, Pitie-Salpetriere Hospital, Paris, France.
Gautam
A M
AM
D000818:Animals; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D018716:Molecular Mimicry / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology*
D006680:HLA Antigens