Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Behçet's disease

Hidekata Yasuoka, Yuka Okazaki, Yutaka Kawakami, Michito Hirakata, Hidetoshi Inoko, Yasuo Ikeda, Masataka Kuwana

研究成果: Article

58 引用 (Scopus)

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Objective. To detect and characterize the autoreactive CD8+ T cells to major histocompatibility complex class 1 chain-related gene A (MICA), a stress-inducible antigen preferentially expressed on the epithelium and endothelium, in patients with Behçet's disease (BD). Methods. A candidate for the antigenic MICA peptide was selected based on its predicted binding affinity for HLA-B51 and proteasomal cleavage sites. Peripheral blood T cells from 14 patients with BD and 15 healthy controls were repeatedly stimulated with the MICA peptide, and the specific T cell response was measured by peptide-induced interferon-γ. Cytotoxic T lymphocyte activity was examined by chromium-51 release from an BLA-151-transfected B cell line in the presence of the MICA peptide. Results. A 9-mer peptide AAAAAIFVI (termed MICA transmembrane [MICA-TM]) was selected as a candidate for the antigenic peptide presented by HLA-B51. A specific T cell response to MICA-TM was detected in 4 patients with BD (29%) but in none of the 15 healthy donors. All 4 responders had HLA-B51 and active disease, and the specific T cell response was lost after the BD-related symptoms disappeared. The MICA-induced T cell response was specifically inhibited by anti-HLA class I antibody or by CD8+ cell depletion. MICA-reactive T cells recognized an HLA-B51-transfected B cell line pulsed with MICA-TM or a B cell line transfected with both HLA-B51 and MICA in the absence of exogenous peptides. Finally, MICA-stimulated T cell lines lysed the HLA-B51-expressing B cell line in the presence of MICA-TM. Conclusion. HLA-B51-restricted cytotoxic T lymphocytes autoreactive to MICA may be involved in the pathogenesis of BD.

元の言語English
ページ(範囲)3658-3662
ページ数5
ジャーナルArthritis and Rheumatism
50
発行部数11
DOI
出版物ステータスPublished - 2004 11

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HLA-B51 Antigen
Cytotoxic T-Lymphocytes
Major Histocompatibility Complex
T-Lymphocytes
Peptides
Genes
Cell Line
B-Lymphocytes
Peptide T
Immunoglobulin Isotypes
Chromium
Interferons
Endothelium
Blood Cells
Epithelium
Tissue Donors
Antigens

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

これを引用

Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Behçet's disease. / Yasuoka, Hidekata; Okazaki, Yuka; Kawakami, Yutaka; Hirakata, Michito; Inoko, Hidetoshi; Ikeda, Yasuo; Kuwana, Masataka.

:: Arthritis and Rheumatism, 巻 50, 番号 11, 11.2004, p. 3658-3662.

研究成果: Article

Yasuoka, Hidekata ; Okazaki, Yuka ; Kawakami, Yutaka ; Hirakata, Michito ; Inoko, Hidetoshi ; Ikeda, Yasuo ; Kuwana, Masataka. / Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Behçet's disease. :: Arthritis and Rheumatism. 2004 ; 巻 50, 番号 11. pp. 3658-3662.
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title = "Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Beh{\cc}et's disease",
abstract = "Objective. To detect and characterize the autoreactive CD8+ T cells to major histocompatibility complex class 1 chain-related gene A (MICA), a stress-inducible antigen preferentially expressed on the epithelium and endothelium, in patients with Beh{\cc}et's disease (BD). Methods. A candidate for the antigenic MICA peptide was selected based on its predicted binding affinity for HLA-B51 and proteasomal cleavage sites. Peripheral blood T cells from 14 patients with BD and 15 healthy controls were repeatedly stimulated with the MICA peptide, and the specific T cell response was measured by peptide-induced interferon-γ. Cytotoxic T lymphocyte activity was examined by chromium-51 release from an BLA-151-transfected B cell line in the presence of the MICA peptide. Results. A 9-mer peptide AAAAAIFVI (termed MICA transmembrane [MICA-TM]) was selected as a candidate for the antigenic peptide presented by HLA-B51. A specific T cell response to MICA-TM was detected in 4 patients with BD (29{\%}) but in none of the 15 healthy donors. All 4 responders had HLA-B51 and active disease, and the specific T cell response was lost after the BD-related symptoms disappeared. The MICA-induced T cell response was specifically inhibited by anti-HLA class I antibody or by CD8+ cell depletion. MICA-reactive T cells recognized an HLA-B51-transfected B cell line pulsed with MICA-TM or a B cell line transfected with both HLA-B51 and MICA in the absence of exogenous peptides. Finally, MICA-stimulated T cell lines lysed the HLA-B51-expressing B cell line in the presence of MICA-TM. Conclusion. HLA-B51-restricted cytotoxic T lymphocytes autoreactive to MICA may be involved in the pathogenesis of BD.",
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T1 - Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Behçet's disease

AU - Yasuoka, Hidekata

AU - Okazaki, Yuka

AU - Kawakami, Yutaka

AU - Hirakata, Michito

AU - Inoko, Hidetoshi

AU - Ikeda, Yasuo

AU - Kuwana, Masataka

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N2 - Objective. To detect and characterize the autoreactive CD8+ T cells to major histocompatibility complex class 1 chain-related gene A (MICA), a stress-inducible antigen preferentially expressed on the epithelium and endothelium, in patients with Behçet's disease (BD). Methods. A candidate for the antigenic MICA peptide was selected based on its predicted binding affinity for HLA-B51 and proteasomal cleavage sites. Peripheral blood T cells from 14 patients with BD and 15 healthy controls were repeatedly stimulated with the MICA peptide, and the specific T cell response was measured by peptide-induced interferon-γ. Cytotoxic T lymphocyte activity was examined by chromium-51 release from an BLA-151-transfected B cell line in the presence of the MICA peptide. Results. A 9-mer peptide AAAAAIFVI (termed MICA transmembrane [MICA-TM]) was selected as a candidate for the antigenic peptide presented by HLA-B51. A specific T cell response to MICA-TM was detected in 4 patients with BD (29%) but in none of the 15 healthy donors. All 4 responders had HLA-B51 and active disease, and the specific T cell response was lost after the BD-related symptoms disappeared. The MICA-induced T cell response was specifically inhibited by anti-HLA class I antibody or by CD8+ cell depletion. MICA-reactive T cells recognized an HLA-B51-transfected B cell line pulsed with MICA-TM or a B cell line transfected with both HLA-B51 and MICA in the absence of exogenous peptides. Finally, MICA-stimulated T cell lines lysed the HLA-B51-expressing B cell line in the presence of MICA-TM. Conclusion. HLA-B51-restricted cytotoxic T lymphocytes autoreactive to MICA may be involved in the pathogenesis of BD.

AB - Objective. To detect and characterize the autoreactive CD8+ T cells to major histocompatibility complex class 1 chain-related gene A (MICA), a stress-inducible antigen preferentially expressed on the epithelium and endothelium, in patients with Behçet's disease (BD). Methods. A candidate for the antigenic MICA peptide was selected based on its predicted binding affinity for HLA-B51 and proteasomal cleavage sites. Peripheral blood T cells from 14 patients with BD and 15 healthy controls were repeatedly stimulated with the MICA peptide, and the specific T cell response was measured by peptide-induced interferon-γ. Cytotoxic T lymphocyte activity was examined by chromium-51 release from an BLA-151-transfected B cell line in the presence of the MICA peptide. Results. A 9-mer peptide AAAAAIFVI (termed MICA transmembrane [MICA-TM]) was selected as a candidate for the antigenic peptide presented by HLA-B51. A specific T cell response to MICA-TM was detected in 4 patients with BD (29%) but in none of the 15 healthy donors. All 4 responders had HLA-B51 and active disease, and the specific T cell response was lost after the BD-related symptoms disappeared. The MICA-induced T cell response was specifically inhibited by anti-HLA class I antibody or by CD8+ cell depletion. MICA-reactive T cells recognized an HLA-B51-transfected B cell line pulsed with MICA-TM or a B cell line transfected with both HLA-B51 and MICA in the absence of exogenous peptides. Finally, MICA-stimulated T cell lines lysed the HLA-B51-expressing B cell line in the presence of MICA-TM. Conclusion. HLA-B51-restricted cytotoxic T lymphocytes autoreactive to MICA may be involved in the pathogenesis of BD.

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