HLA-DRB 1 Polymorphism Determines Susceptibility to Autoimmune Thyroiditis in Transgenic Mice : Definitive Association with HLA-DRBI * 0301 ( DR 3 ) Gene

Familial clustering of auto immune thyroid diseases has led to studies of their association with human major histocompatibility complex (MHC) class II genes. One such gene implicated in Hashimoto 's thyroiditis (HT) is H L A D R 3 , but the association is weak and is contradicted by other reports. O n the other hand, murine experimental auto immune thyroiditis (EAT), a model for HT, presents a clear linkage with M H C class II. Moreover, it is inducible with thyroglobulin (Tg), the common autoantigen in either species. Immunization of HLA-DRBI*0301 (DR3) transgenic mice with mouse or human Tg resulted in severe thyroiditis. In contrast, transgenic mice expressing the H L A D R B I * 1 5 0 2 (DR2) gene were resistant to EAT. Our studies show that H L A D R B 1 polymorphism determines susceptibility to auto immune thyroiditis and implicate Tg as an important autoantigen.

[1]  G. Schönrich,et al.  Negative and positive selection by HLA-DR3(DRw17) molecules in transgenic mice , 2004, Immunogenetics.

[2]  K. Beisel,et al.  Regulation of experimental autoimmune thyroiditis: Mapping of susceptibility to the I-A subregion of the mouse H-2 , 2004, Immunogenetics.

[3]  H. Inoko,et al.  Human leukocyte antigen-DRB1*1502 (DR2Dw12) transgene reduces incidence and severity of arthritis in mice. , 1996, Human immunology.

[4]  H. Luthra,et al.  HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel model for human polyarthritis , 1996, The Journal of experimental medicine.

[5]  Q. Wan,et al.  Primary hormonogenic sites as conserved autoepitopes on thyroglobulin in murine autoimmune thyroiditis. Secondary role of iodination. , 1995, Journal of immunology.

[6]  M. Zou,et al.  Typing for major histocompatibility complex class II antigens in thyroid tissue blocks: association of Hashimoto's thyroiditis with HLA-DQA0301 and DQB0201 alleles. , 1992, The Journal of clinical endocrinology and metabolism.

[7]  J. Franklyn,et al.  HLA class II gene polymorphism contributes little to Hashimoto's thyroiditis , 1992, Clinical endocrinology.

[8]  S. Wallenstein,et al.  Genetics of autoimmune thyroid disease: lack of evidence for linkage to HLA within families. , 1992, The Journal of clinical endocrinology and metabolism.

[9]  H. Waldmann,et al.  Suppression in murine experimental autoimmune thyroiditis: in vivo inhibition of CD4+ T cell-mediated resistance by a nondepleting rat CD4 monoclonal antibody. , 1991, Cellular immunology.

[10]  D. Gray,et al.  Mice lacking MHC class II molecules , 1991, Cell.

[11]  A. Weetman,et al.  HLA Associations with Hashimoto's thyroiditis , 1991, Clinical endocrinology.

[12]  G. Nabozny,et al.  Suppression in experimental autoimmune thyroiditis: the role of unique and shared determinants on mouse thyroglobulin in self-tolerance. , 1990, Cellular immunology.

[13]  K. Badenhoop,et al.  Susceptibility to thyroid autoimmune disease: molecular analysis of HLA-D region genes identifies new markers for goitrous Hashimoto's thyroiditis. , 1990, The Journal of clinical endocrinology and metabolism.

[14]  P. A. Peterson,et al.  Transgenic HLA-DRα faithfully reconstitutes IE-controlled immune functions and induces cross-tolerance to Eα in Eα 0 mutant mice , 1989, Cell.

[15]  H. Inoko,et al.  Analysis of gene structure and antigen determinants of DR2 antigens using DR gene transfer into mouse L cells. , 1989, Journal of immunology.

[16]  N. Farid,et al.  ASSOCIATION OF GOITROUS AUTOIMMUNE THYROIDITIS WITH HLA‐DR3 IN EASTERN HUNGARY , 1987, Journal of immunogenetics.

[17]  J. Buerstedde,et al.  Characterization of cell lines expressing mutant I-Ab and I-Ak molecules allows the definition of distinct serologic epitopes on A alpha and A beta polypeptides. , 1986, Journal of immunology.

[18]  R. Smallridge,et al.  Goitrous Hashimoto's thyroiditis. Lack of association with HLA antigens. , 1986, Molecular biology & medicine.

[19]  C. David,et al.  Characterization of the in vitro murine T-cell proliferative responses to murine and human thyroglobulins in thyroiditis-susceptible and -resistant mice. , 1985, Cellular immunology.

[20]  H. Bliddal,et al.  HLA-D in Hashimoto's thyroiditis. , 2008, Tissue antigens.

[21]  M. Loken,et al.  Flow cytometry as an analytical and preparative tool in immunology. , 1982, Journal of immunological methods.

[22]  N. Farid,et al.  The association of goitrous autoimmune thyroiditis with HLA-DR5. , 2008, Tissue antigens.

[23]  W. Mayr,et al.  HLA-DR and Hashimoto's thyroiditis. , 2008, Tissue antigens.

[24]  D. Charron,et al.  HLA-DR epitope region definition by use of monoclonal antibody probes. , 1980, Journal of immunology.

[25]  K. Ozato,et al.  Monoclonal antibodies to mouse MHC antigens. II. Antibodies to the H-2Ld antigen, the products of a third polymorphic locus of the mouse major histocompatibility complex. , 1980, Journal of immunology.

[26]  K. Ozato,et al.  Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. , 1980, Journal of immunology.

[27]  N. Rose,et al.  Regulation of autoimmune response to mouse thyroglobulin: influence of H-2D-end genes. , 1979, Journal of immunology.

[28]  N. Farid,et al.  Hashimoto's thyroiditis is associated with HLA-DRw3. , 1978, The New England journal of medicine.