Immunogenetics of collagen-induced arthritis.
CIA is a unique experimental model of disease, which may be particularly relevant to the study of RA, since it represents a true autoimmune reaction against a major joint component. Since it represents a model of the association of MHC genes and disease, it has a broad relevance to the study of disease, particularly the contribution of class II MHC genes to autoimmunity. This disease model has been demonstrated in three species, and a marked influence of immunogenetic control is apparent. Native type II collagen is a large protein with a genetically conserved structure, giving rise to a number of cross-reactive antigen epitopes between species. Susceptibility to CIA correlates with an Ir directed against certain epitopes, and this autoimmune response appears to be controlled by MHC-linked genes. In the mouse, susceptibility has been specifically associated with variations in the I-A beta chain. The immunogenetic control may be effected through the T-cell recognition of the collagen molecule, resulting in antibodies and reactive cells with a specificity for native autologous type II collagen. Although the specificity of the anti-type II collagen response is the critical element in the generation of the autoimmune reaction, production of a high level of antibody is important, as well as a complement-fixing isotype. Cell-mediated immunity to type II collagen contributes to the disease chronicity, either through the generation of inappropriate T help, or a suppressor defect, and the production of factors. However, the precise sequence of events, from antigen recognition to joint damage, has yet to be elucidated fully. Some aspects of this experimental model bear a striking resemblence to RA. Hopefully, this experimental model will provide valuable insights into the significance of collagen autoimmunity and the contribution of class II genes to the pathology of arthritic disease.
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D003094:Collagen / Q000633:toxicity*; D004195:Disease Models, Animal / Q000235:genetics / Q000276:immunology*; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D011323:Primates; D051381:Rats
D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C038353:histocompatibility antigens RT, rat; D003094:Collagen