Multiple sclerosis: MHC associations and therapeutic implications.
Multiple sclerosis (MS) is an autoimmune disease with an important genetic component. The strongest genetic association is with the major histocompatibility complex (MHC) region. Several MHC alleles predispose to the disease, the most prominent of which are certain alleles in the HLA-DR2 haplotype. Functional and structural studies have helped to explain the molecular basis of these associations. Although there is currently no curative treatment for MS, an increased understanding of the disease has aided the design of immunotherapies that act on the immune system more specifically than the longstanding drugs. Many of these therapies work at the antigen-specific level, disrupting the interaction between T-cell receptors and MHC molecules that leads to disease.
Holmes
Samantha
S
Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, The University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK. samantha.holmes@ccc.ox.ac.uk
Friese
Manuel A
MA
Siebold
Christian
C
Jones
E Yvonne
EY
Bell
John
J
Fugger
Lars
L
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D015802:HLA-DR2 Antigen / Q000235:genetics / Q000276:immunology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D047589:Leukocyte Reduction Procedures; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
D001324:Autoantigens; D015802:HLA-DR2 Antigen; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell