Molecular and cellular analyses of HLA class II-associated susceptibility to autoimmune diseases in the Japanese population

Yasuharu Nishimura, Hiroshi Ito, Shinji Fujii, Hiroki Tabata, Yoshiaki Tokano, Yu Zhen Chen, Ichiro Matsuda, Hiroaki Mitsuya, Jun-Ichi Kira, Hiroshi Hashimoto, Satoru Senju, Sho Matsushita

研究成果: ジャーナルへの寄稿評論記事

抄録

It is well known that individuals who are positive for particular HLA class II alleles show a high risk of developing autoimmune diseases. HLA class II molecules expressed on antigen-presenting cells present antigenic peptides to CD4 + T cells. Their extensive polymorphism affects the structures of peptides bound to HLA class II molecules to create individual differences in immune responses to antigenic peptides. In order to gain a better understanding of mechanisms of the association between HLA class II alleles and susceptibility to autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative T cells. Many of the autoimmune diseases are observed in all ethnic groups, whereas the incidence of diseases, clinical manifestations and disease-susceptible HLA class II alleles are different among various ethnic groups for some autoimmune diseases. These phenomena suggest that differences in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may cause these differences. Therefore, comparisons among disease-susceptible HLA class II alleles, autoantigenic peptides, and clinical manifestations of autoimmune diseases in different ethnic groups would be helpful in elucidating the pathogenesis of the diseases. In this review, we describe our recent findings on (1) the uniqueness of both clinical manifestations and the HLA-linked genetic background of Asian-type (opticospinal form) multiple sclerosis, (2) the characteristics of glutamic acid decarboxylase 65 (GAD65) or β 2 -glycoprotein I (β 2 -GPI) autoreactive T cells in Japanese patients with insulin-dependent diabetes mellitus (IDDM) or anti-β 2 -GPI antibody-associated autoimmunity, respectively, and (3) the generation of an efficient delivery system of peptides to the HLA class II-restricted antigen presentation pathway by utilizing a class II-associated invariant chain peptide (CLIP)-substituted invariant chain, which may be applicable to an evaluation of the "molecular mimicry hypothesis" for the activation of autoreactive T cells.

元の言語英語
ページ(範囲)103-112
ページ数10
ジャーナルModern Rheumatology
11
発行部数2
DOI
出版物ステータス出版済み - 12 1 2001

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Autoimmune Diseases
Peptides
Population
Alleles
Ethnic Groups
T-Lymphocytes
Glycoproteins
Molecular Mimicry
Glutamate Decarboxylase
Histocompatibility Antigens Class II
Antigen Presentation
Antigen-Presenting Cells
HLA Antigens
Autoimmunity
Type 1 Diabetes Mellitus
Individuality
Antibodies
Incidence
invariant chain

All Science Journal Classification (ASJC) codes

  • Rheumatology

これを引用

Molecular and cellular analyses of HLA class II-associated susceptibility to autoimmune diseases in the Japanese population. / Nishimura, Yasuharu; Ito, Hiroshi; Fujii, Shinji; Tabata, Hiroki; Tokano, Yoshiaki; Chen, Yu Zhen; Matsuda, Ichiro; Mitsuya, Hiroaki; Kira, Jun-Ichi; Hashimoto, Hiroshi; Senju, Satoru; Matsushita, Sho.

:: Modern Rheumatology, 巻 11, 番号 2, 01.12.2001, p. 103-112.

研究成果: ジャーナルへの寄稿評論記事

Nishimura, Y, Ito, H, Fujii, S, Tabata, H, Tokano, Y, Chen, YZ, Matsuda, I, Mitsuya, H, Kira, J-I, Hashimoto, H, Senju, S & Matsushita, S 2001, 'Molecular and cellular analyses of HLA class II-associated susceptibility to autoimmune diseases in the Japanese population', Modern Rheumatology, 巻. 11, 番号 2, pp. 103-112. https://doi.org/10.1007/s101650170020
Nishimura, Yasuharu ; Ito, Hiroshi ; Fujii, Shinji ; Tabata, Hiroki ; Tokano, Yoshiaki ; Chen, Yu Zhen ; Matsuda, Ichiro ; Mitsuya, Hiroaki ; Kira, Jun-Ichi ; Hashimoto, Hiroshi ; Senju, Satoru ; Matsushita, Sho. / Molecular and cellular analyses of HLA class II-associated susceptibility to autoimmune diseases in the Japanese population. :: Modern Rheumatology. 2001 ; 巻 11, 番号 2. pp. 103-112.
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abstract = "It is well known that individuals who are positive for particular HLA class II alleles show a high risk of developing autoimmune diseases. HLA class II molecules expressed on antigen-presenting cells present antigenic peptides to CD4 + T cells. Their extensive polymorphism affects the structures of peptides bound to HLA class II molecules to create individual differences in immune responses to antigenic peptides. In order to gain a better understanding of mechanisms of the association between HLA class II alleles and susceptibility to autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative T cells. Many of the autoimmune diseases are observed in all ethnic groups, whereas the incidence of diseases, clinical manifestations and disease-susceptible HLA class II alleles are different among various ethnic groups for some autoimmune diseases. These phenomena suggest that differences in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may cause these differences. Therefore, comparisons among disease-susceptible HLA class II alleles, autoantigenic peptides, and clinical manifestations of autoimmune diseases in different ethnic groups would be helpful in elucidating the pathogenesis of the diseases. In this review, we describe our recent findings on (1) the uniqueness of both clinical manifestations and the HLA-linked genetic background of Asian-type (opticospinal form) multiple sclerosis, (2) the characteristics of glutamic acid decarboxylase 65 (GAD65) or β 2 -glycoprotein I (β 2 -GPI) autoreactive T cells in Japanese patients with insulin-dependent diabetes mellitus (IDDM) or anti-β 2 -GPI antibody-associated autoimmunity, respectively, and (3) the generation of an efficient delivery system of peptides to the HLA class II-restricted antigen presentation pathway by utilizing a class II-associated invariant chain peptide (CLIP)-substituted invariant chain, which may be applicable to an evaluation of the {"}molecular mimicry hypothesis{"} for the activation of autoreactive T cells.",
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AU - Tokano, Yoshiaki

AU - Chen, Yu Zhen

AU - Matsuda, Ichiro

AU - Mitsuya, Hiroaki

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