T Cell Response with Stress Proteins

T 细胞对应激蛋白的反应

• 批准号: 09470067
• 负责人: SATO Noriyuki
• 金额: $ 8.19万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470067/
• 关键词: hsp70; molecular chaperones; T cells; antigenic peptides; polyamines; MHC class I; TAP; rat TCR Vδ6; HSP70; TCRγδ; 細胞表面発現; 単クローン抗体; hsp 70; TCR; γδ T cell; ハイブリドーマ

Our study indicated the important role of the 70 kA heat shock proteins (hsp70) for feeding the major histocompatibility antigen complexes (MHC) class I-bound antigenic peptides to the transporters associated with the antigen processing (TAP), and revealed a novel possibility that the repertoire of MHC class I-bound peptides may be limited, at least in part, in the cytosol by their affinity to molecular chaperone hsp70. We also indicated an involvement of polyamines in the interaction between hsp70 and TAP, suggesting the possible role of polyamines in the tumor escape mechanisms.It was also suggested that some form of hsp70 is expressed on the cell surface with as yet unknown mechanism. Our current data support the notion that an hsp70-like molecule could be presented together with the cellular peptides antigens to particular T cells with the T-cell receptor (TCR) γδ chains. Since the expression of this hsp70-like molecule on the cell surface is usually induced along with cell transformation by activated oncogenes, it is likely that T cells with the TCR Vδ6 family contribute to the host's resistance to tumor cells.

我们的研究表明 70 kA 热休克蛋白 (hsp70) 在将主要组织相容性抗原复合物 (MHC) I 类结合抗原肽输送给与抗原加工 (TAP) 相关的转运蛋白方面发挥着重要作用，并揭示了一种新的可能性： MHC I 类结合肽的全部成分可能（至少部分地）由于其与分子伴侣 hsp70 的亲和力而受到限制。 hsp70 和 TAP 之间的相互作用，表明多胺在肿瘤逃逸机制中可能发挥作用。还表明某种形式的 hsp70 在细胞表面表达，但我们目前的数据支持 hsp70 样的观点。由于这种 hsp70 样分子在细胞表面的表达通常与细胞一起被诱导，因此该分子可以与细胞肽抗原一起呈递给具有 T 细胞受体 (TCR) γδ 链的特定 T 细胞。通过激活的癌基因进行转化，具有 TCR Vδ6 家族的 T 细胞很可能有助于宿主对肿瘤细胞的抵抗。

项目成果

Suzuki,K., Sahara,H., Okada,Y., Hirata,K., Kikuchi,K., Sato,N.: "Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoic T lymphocytes."J. Immunol.. 163. 2783-2791 (1999)

Suzuki,K.、Sahara,H.、Okada,Y.、Hirata,K.、Kikuchi,K.、Sato,N.：“由 HLA-A31 识别的人胃印戒细胞癌天然抗原肽的鉴定

Maeda,A., Ohguro,H., Maeda,T., Sato,N., Kuroki,Y., Nakagawa,T.: "Aberrant expression of photoreceptor specific calcium binding protein (recoverin) in cancer cell lines."Cancer. Res.,. (2000)

Maeda,A.、Ohguro,H.、Maeda,T.、Sato,N.、Kuroki,Y.、Nakakawa,T.：“癌细胞系中光感受器特异性钙结合蛋白（恢复蛋白）的异常表达。”癌症。

Nagata,M.,Akazawa,T.,Tamura,Y.,Sagae,S.,Kudo,R.,Sato,N.et al: "The expression of a novel natural killer inhibitory molecule,Cho-1,on the chorionic cytotrophoblast cells of successful pregnancy,but not of spontaneous abortion."Clin.Exp.Immunol.. (in press)

Nagata,M.,Akazawa,T.,Tamura,Y.,Sagae,S.,Kudo,R.,Sato,N.等：“一种新型自然杀伤抑制分子 Cho-1 在绒毛膜上的表达

Suzuki,K.,Sahara,H.,Okada,Y.,Hirata,K.,Kikuchi,K.,Sato,N.et al: "Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoic T lymphocytes."J.Immunol.. 163. 2783-2791 (1999)

Suzuki,K.,Sahara,H.,Okada,Y.,Hirata,K.,Kikuchi,K.,Sato,N.等人：“通过 HLA- 识别人胃印戒细胞癌的天然抗原肽的鉴定

Hirai,I.,Sato,N.,Kikuchi,K.et al: "Localization of pNT22 70kDa heat shock cognate-like protein in the plasma membrane." Exp.Cell Res.(submitted).

Hirai,I.、Sato,N.、Kikuchi,K.等人：“pNT22 70kDa 热休克同源样蛋白在质膜中的定位。”