2003 Fiscal Year Annual Research Report

腸管免疫におけるマウスTL抗原の役割と炎症性腸疾患への関与の検索

Research Project

Project/Area Number	14570293
Research Institution	Aichi Cancer Center Research Institute
Principal Investigator	辻村邦夫愛知県がんセンター, 腫瘍免疫学部, 室長 (10227407)
Co-Investigator(Kenkyū-buntansha)	小幡裕一理化学研究所, バイオリソースセンター, 部長 (30177290)
Keywords	TL抗原 / CTL / テトラマー
Research Abstract	TL抗原は主要組織適合抗原(MHC)クラスIb群に属し、すべてのマウスの腸上皮細胞に発現する。また正常胸腺においては、TL抗原を発現するマウス(A系等)と発現しないマウス(C3H等)がある。腸管に発現するTL抗原の生理的機能を明らかにするため、その抗原提示機能をTL抗原特異的CTL指標をして検索を行なった。 TL抗原特異的CTLの抗原認識機構を明らかにするため、大腸菌由来のリコンビナント蛋白であるT3^b-TLとβ_2Mを用いて、抗原物質を添加せずにTLテトラマーを作成した。本テトラマーがTL抗原特異的CTLと反応性を示すことより、これらCTLはTL分子と抗原物質により形成されるエピトープではなく、Framework自身を認識していることが示された。本テトラマーが、Bulk CTL lineの大部分を染色したことから、TL抗原特異的CTLの大部分はTL分子に提示される抗原分子非依存性にTL抗原を認識していることが予想された。 TL抗原はMHCクラスIa群に比べ多型性が少なく、抗原提示能を有するとすれば、通常のペプチド以外の物質(あるいは特殊なペプチド)を提示すると予想されていた。しかしながら、今回得られた知見は、TL抗原が抗原提示分子として機能している可能性が低いことを示唆している。TL分子のペプチド結合溝はMHCクラスIa群に比べ非常に狭く、抗原分子を提示している可能性が低いという、我々の予想を示唆する結晶解析の実験結果が最近報告された。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Kuzushima, K., et al.: "Tetramer-assisted identification and characterization of epitopes recognized by HLA A^*2402-resiricted Epstein-Barr virus-specific CD8^+ T cells."Blood. 101. 1460-1468 (2003)
[Publications] Akatsuka, Y, et al.: "Identification of a polymorphic gene, BCL2A1,encoding two novel hematopoietic lineage specific minor histocompatibility antigens."Journal of Experimental Medicine. 197. 1489-1500 (2003)
[Publications] Miyazaki, M., et al.: "Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells."Clinical Immunology. 107. 198-201 (2003)
[Publications] Tsujimura, K., et al.: "Thymus leukemia antigen (TL)-specific CTL recognize α1/α2 domain of TL free from antigenic peptides."International Immunology. 15. 1319-1326 (2003)
[Publications] Ito, T., et al.: "Alterations of immune functions in barrier disrupted by UVB irradiation."Journal of Dermatological Science. 33. 151-159 (2003)
[Publications] Tahtis, K., et al.: "Expression and targeting of human fibroblast activation protein in a human skin/severe combined immunodeficient mouse breast cancer xenograft model."Molecular Cancer Therapy. 2. 729-737 (2003)
[Publications] Saito, S., et al.: "Generation of cloned calves and transgenic chimeric embryos from bovine embryonic stem-like cells."Biochemical and Biophysical Research Communications. 309. 104-113 (2003)
[Publications] Tajima, K., et al.: "Expression of cancer/testis (CT) antigens in lung cancer."Lung Cancer. 42. 23-33 (2003)
[Publications] Park, E.J.., et al.: "Clonal expansion of double-positive intraepithelial lymphocytes by MHC class I-related chain A expressed in mouse small intestinal epithelium."Journal of Immunology. 171. 4131-4139 (2003)
[Publications] Kondo, E., et al.: "Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles."Blood. 103. 630-638 (2004)
[Publications] Akazawa, T., et al.: "Adjuvant-mediated tumor regression and tumor-specific CTL induction are impaired in MyD88-deficient mice."Cancer Research. 64. 757-764 (2004)
[Publications] Nishida, T., et al.: "Clinical relevance of a newly identified HLA-A24-restricted minor histocompatibility antigen epitope derived from BCL2A1, ACC-1, in patients receiving HLA genotypically matched unrelated bone marrow transplant."British Journal of Hematology. 124. 629-635 (2004)
[Publications] Tajima, K., et al.: "Interferon-γ differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes."International Journal of Cancer. 発表予定. (2004)
[Publications] Tsujimura, K., et al.: "Thymus-leukemia (TL) antigen as a majorhistocompatibility complex (MHC) class IB molecule and tumor specific antigen."Cancer Science. 発表予定. (2004)

2003 Fiscal Year Annual Research Report

腸管免疫におけるマウスTL抗原の役割と炎症性腸疾患への関与の検索

Principal Investigator

辻村 邦夫 愛知県がんセンター, 腫瘍免疫学部, 室長 (10227407)

Research Products

[Publications] Kuzushima, K., et al.: "Tetramer-assisted identification and characterization of epitopes recognized by HLA A^*2402-resiricted Epstein-Barr virus-specific CD8^+ T cells."Blood. 101. 1460-1468 (2003)

[Publications] Akatsuka, Y, et al.: "Identification of a polymorphic gene, BCL2A1,encoding two novel hematopoietic lineage specific minor histocompatibility antigens."Journal of Experimental Medicine. 197. 1489-1500 (2003)

[Publications] Miyazaki, M., et al.: "Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells."Clinical Immunology. 107. 198-201 (2003)

[Publications] Tsujimura, K., et al.: "Thymus leukemia antigen (TL)-specific CTL recognize α1/α2 domain of TL free from antigenic peptides."International Immunology. 15. 1319-1326 (2003)

[Publications] Ito, T., et al.: "Alterations of immune functions in barrier disrupted by UVB irradiation."Journal of Dermatological Science. 33. 151-159 (2003)

[Publications] Tahtis, K., et al.: "Expression and targeting of human fibroblast activation protein in a human skin/severe combined immunodeficient mouse breast cancer xenograft model."Molecular Cancer Therapy. 2. 729-737 (2003)

[Publications] Saito, S., et al.: "Generation of cloned calves and transgenic chimeric embryos from bovine embryonic stem-like cells."Biochemical and Biophysical Research Communications. 309. 104-113 (2003)

[Publications] Tajima, K., et al.: "Expression of cancer/testis (CT) antigens in lung cancer."Lung Cancer. 42. 23-33 (2003)

[Publications] Park, E.J.., et al.: "Clonal expansion of double-positive intraepithelial lymphocytes by MHC class I-related chain A expressed in mouse small intestinal epithelium."Journal of Immunology. 171. 4131-4139 (2003)

[Publications] Kondo, E., et al.: "Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles."Blood. 103. 630-638 (2004)

[Publications] Akazawa, T., et al.: "Adjuvant-mediated tumor regression and tumor-specific CTL induction are impaired in MyD88-deficient mice."Cancer Research. 64. 757-764 (2004)

[Publications] Nishida, T., et al.: "Clinical relevance of a newly identified HLA-A24-restricted minor histocompatibility antigen epitope derived from BCL2A1, ACC-1, in patients receiving HLA genotypically matched unrelated bone marrow transplant."British Journal of Hematology. 124. 629-635 (2004)

[Publications] Tajima, K., et al.: "Interferon-γ differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes."International Journal of Cancer. 発表予定. (2004)

[Publications] Tsujimura, K., et al.: "Thymus-leukemia (TL) antigen as a majorhistocompatibility complex (MHC) class IB molecule and tumor specific antigen."Cancer Science. 発表予定. (2004)

辻村邦夫愛知県がんセンター, 腫瘍免疫学部, 室長 (10227407)