Abstract
HLA class II alleles can protect against immunological diseases. Seeking an animal model for a naturally occurring protective allele, we screened a panel of H2-congenic and recombinant mouse strains for ability to protect against collagen-induced arthritis. The strains were crossed with the susceptible strain DBA/1, and the F1 hybrids immunized with cattle and chicken type II collagen. Hybrids having the H2A b allele displayed a reduced incidence and duration of the disease. They also had a reduced level of pre-disease inflammation, but not of anti-collagen antibodies. The allele is already known to be associated with reduction of other apparently unrelated immune responses, suggesting that some form of functional differentiation may operate that is not exclusively related to epitope-binding. It is suggested that this may reflect allelic variation in the class II major histocompatibility complex promoter region.
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Altmann, D. M., Dansom, S. D., and Marsh, S. G. E. What is the basis for HLA-DQ associations with autoimmune disease? Immunol Today 12: 267–270, 1991
Baisch, J. M., Weeks, T., Giles, R., Hoover, M., Stasny, P., and Capra, J. D. Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. New Engl J Med 322: 1836–1841, 1990
Bohme, J., Schuhbaur, B., Kanagawa, O., Benoist, C., and Mathis, D. MHC-linked protection from diabetes dissociated from clonal deletion of T cells. Science 249: 293–295, 1990
Brunner, M. C., Mitchison, N. A., and Schneider, S. C. The integrative activity of the immune system. Scand J Immunol 40: 579–580, 1944
Deighton, C. M., Cavanagh, G., Rigby, A. S., Lloyd, H. L., and Walker, D. J. Both inherited HLA-haplotypes are important in the predisposition to rheumatoid arthritis. Br J Rheumatol 32: 893–898, 1993
Dietrich, A., Mitchison, N. A., Rajnavölgyi, E., and Schneider, S. C. Desequestration of an autoantigen by activated lymphocytes. J Autoimmunity 7: 601–609, 1994
Hirayama, K., Matsushita, S., Kikuchi, I., Iuchi, M., Ohta, N., and Sasazuki, T. HLA-DQ is epistatic to HLA-DR in controling the immune response to schistosomal antigen in humans. Nature 327: 426–430, 1987
Hirose, S., Zhang, D., Nozawa, S., Nishimura, H., and Shirai, T. The I-E linked subregion down-regulates autoimmunity in NZB × NZW F1 mice. Immunogenetics 40: 150–153, 1994
Holmdahl, R., Andersson, M., Goldschmidt, T. J., Gustafsson, K., Jansson, L., and Mo, J. A. Type II collagen autoimmunity in animals and provocations leading to arthritis. Immunol Rev 118: 193–232, 1990
Holmdahl, R., Karlsson, M., Andersson, M. E., Rask, L., and Andersson, L. Localization of a critical restriction site on the I-Ab chain that determines susceptibility to collagen-induced arthritis in mice. Proc Natl Acad Sci USA 86: 9475–9479, 1989
Ivanyi, J. and Sharp, K. Control by H-2 genes of murine antibody responses to protein antigens of Mycobacterium tuberculosis. Immunology 59: 329–332, 1986
Jansson, L. and Holmdahl, R. Oestrogen induced suppression of collagen arthritis. VI. 17β-oestradiol is therapeutically active in normal and castrated F1 hybrid mice of both sexes. Clin Exp Immunol 89: 446–451, 1992
Jarequemada, D., Ollier, W., Awad, J., Young, A., Silman, A., Roitt, I. M., Corbett, M., Hay, F., Cosh, J. A., and Maini, R. N. HLA and rheumatoid arthritis: a combined analysis of 440 British patients. Ann Rheum Dis 45: 627–636, 1986
Klareskog, L. and Olsson, T. Autoimmunity to collagen II and myelin basic protein: comparative studies in human and rodents. Immunol Rev 118: 285–310, 1990
Klein, J. Congenic and segregating inbred strains: immunologically important loci. In M. F. Lyon and A. G. Searle (eds.): Genetic Variants and Strains of the Laboratory Mouse, pp. 797–825, Oxford University Press, Oxford, 1989
Kockum, I., Wassmuth, R., Holmberg, E., Michelsen, B., and Lernmark, A. HLA-DQ primarily confers protection and HLA-DR susceptibility in Type I (insulin-dependent) diabetes studied in population-based affected families and controls. Am J Hum Genet 53: 150–167, 1993
Lang, B., Melchers, I., Urtlacher, A., Tanzi-Fetta, R. F., Kohlbrenner, S., Togio, M. M., and Peters, H. H. HLA-DR1 and DRw6 association in DR-4 negative rheumatoid arthritis patients. Rheumatol Int 10: 171–175, 1990
Lightstone, E., Marvel, J., and Mitchison, N. A. Memory in helper T cells of minor histocompatibility antigens, revealed in vivo by alloimmunization in combination with Thy-1 antigen. Eur J Immunol 22: 115–122, 1992
Louis, P., Eliaou, J. F., Kerlon-Candon, S., Pinet, V., Vincent, R., and Clot, J. Polymorphism in the regulatory region of HLA-DRB genes correlating with haplotype evolution. Immunogenetics 38: 21–26, 1993
Mehra, N. K., Taneja, V., and Kanga, U. Immunogenetics of rheumatic diseases in India. In Proceedings of the fourth ASEAN Congress of Rheumatology, pp. 55–60, Communications Consultants, Singapore, 1993
Meyer-Delius, M., Mitchison, N. A., Pitt-Rivers, R., and Rüde, E. Synthesis of a radioiodine-labelled 2,4-dinitrophenyl hapten and its use for binding assays. Eur J Immunol 1: 267–271, 1971
Miesel, R., Dietrich, A., Ulbrich, N., Kroeger, H., and Mitchison, N. A. Assessment of collagen type II induced arthritis in mice by whole blood chemiluminescence. Autoimmunity, in press
Mitchison, N. A. Specialization, tolerance, memory, competition, latency and strife among T cells. Annu Rev Immunol 10: 1–12, 1992
Mitchison, N. A. and Simon, K. Dominant unresponsiveness controlled by H-2Ab. A new pattern displayed by Thy-1 antigen and F liver antigen. Immunogenetics 32: 104–109, 1990
Nepom, G. T. A unified hypothesis for the complex genetics of HLA associations with type I diabetes. Diabetes 39: 1153–1157, 1990
Oliveria, D. G. B. and Mitchison, N. A. Immune suppression Genes. Clin Exp Immunology 75: 167–177, 1989
Ollier, W., Silman, A., Gosnell, N., Currey, H., Awad, J., Doyle, P., McCloskey, D., Alonso, A., Hossain, M. A., and Festenstein, H. HLA and rheumatoid arthritis: analysis of multicase families. Dis Markers 4: 85–98, 1986
Paul, C., Schoenwald, U., Truckenbrodt, H., Bettinotti, M. P., Bruennler, G., Keller, E., Nevinny-Stickel, C., Yao, Z., and Albert, E. A. HLA-DP/DR interaction in early onset pauciarticular juvenile chronic arthritis. Immunogenetics 37: 442–448, 1993
Rigby, A. S., Silman, A. J., Voelm, L., Gregory, J. C., Ollier, W. E., Khan, M. A., Nepom, G. T., and Thomson, G. Investigating the HLA component in rheumatoid arthritis: an additive (dominant) mode of inheritance is rejected, a recessive mode is preferred. Genet Epidemiol 8: 153–175, 1991
Rihova, B., Riha, I. O., Rossmann, P., and Vetvicka, V. Low IgG response of the mouse strain C57BL/10ScSn after immunization with protein antigens. Folia Microbiol (Praha) 30: 295–301, 1985
Robertson, K., Simon, K., Schneider, S., Timms, E., and Mitchison, A. Tolerance of self induced in thymus organ culture. Eur J Immunol 22: 207–211, 1992
Schwartz, R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol 3: 237–261, 1985
Silver, D. M., McKenzie, I. F., and Winn, H. J. Variation in the response of C57BL-10J and A-J mice to sheep red blood cells. J Exp Med 136: 1063–1071, 1972
Simon, K. A., Seipelt, E., and Sieper, J. Divergent T cell cytokine patterns in inflammatory arthritides. Proc Natl Acad Sci USA, 1994
Stastny, P., Ball, E. J., Khan, M. A., Olsen, N. J., Pincus, T., and Gao, X. HLA-DR4 and other genetic markers in rheumatoid arthritis. Br J Rheumatol 27 (Suppl 2): 132–138, 1988
Thomson, G., Robinson, W. P., Kuhner, M. K., Joe, S., MacDonald, M. J., Gottschall, J. L., Barbosa, J., Rich, S., Bertrams, J., Buar, M. P., Partanen, J., Tait, B. D., Schober, E., Mayr, W. R., Ludvigsson, J., Lindbolm, B., Farid, N. R., Thompson, G., and Deschamps, I. Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus. Am J Hum Genet 43: 799–816, 1988
Van Vollenhoven, R. F., Thorbecke, G. J., and Siskind, G. W. Exposure of female mice to type II collagen reduces susceptibility to collagen-induced arthritis in offspring. Eur J Immunol 20: 2149–2152, 1990
Walker, D. J. and Griffiths, I. D. HLA associations are with severe rheumatoid arthritis. Dis Markers 4: 121–132, 1986
Wooley, P. H. Collagen-induced arthritis in the mouse. Meth Enzymol 162: 361–373, 1988
Wooley, P. H., Luthra, H. S., Stuart, J. M., and David, C. S. Type II collagen-induced arthritis in mice. Major histocompatibility complex (I region) linkage and antibody response. J Exp Med 154: 688–700, 1981
Yao, Z., Kimura, A., Hartung, K., Haas, P. J., Volgger, A., Brunnler, G., Bonisch, J., and Albert, E. D. Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in systemic lupus erythematosus. Immunogenetics 38: 421–429, 1993
Zeliszewski, D., Tiercy, J.-M., Boitard, C., Gu, X.-F., Loche, M., Krisnamoorthy, R., Simonney, N., Elion, J., Bach, J.-F., Mach, B., and Sterkers, G. Extensive study of DRB, DQA, and DQB gene polymorphism in 23 DR2-positive, insulin-dendent diabetes mellitus patients. Hum Immunol 33: 140, 1992
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Mitchison, N.A., Brunner, M.C. Association of H2A b with resistance to collagen-induced arthritis in H2-recombinant mouse strains: an allele associated with reduction of several apparently unrelated responses. Immunogenetics 41, 239–245 (1995). https://doi.org/10.1007/BF00172065
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DOI: https://doi.org/10.1007/BF00172065