Identification of the ligand recognized by a mAb specific for CD4^+CD8^+ thymocyte

CD4^ CD8^ 胸腺细胞特异性 mAb 识别的配体的鉴定

• 批准号: 11670325
• 负责人: FUKUI Yoshinori
• 金额: $ 2.43万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670325/
• 关键词: T cell differentiation; CD4^+CD8^+ thymocytes; TCR; MHC; self peptides; positive selection; Thy1 molecule; 単クローン抗体; TCR-MHC; ペプチド複合体相互作用; アポトーシス; Thy-1

Although the diversity of αβ T cell receptors (TCRs) theoretically reaches 10^<15> by random rearrangement of five gene segments and random nucleotide addition, mature T cells express highly selected TCRs in that they exhibit tolerance to self-antigenic peptides and restriction by self-MHC molecules. This mainly results from two reciprocal selection processes, positive and negative selection, acting at CD4^+CD8^+ stage during T cell development in the thymus. With the use of the mAb specific for CD4^+CD8^+ thymocytes, we found that CD4^+CD8^+ thymocytes lacking TCR- MHC/peptide complex interaction specifically express multimerized Thy1 molecules. On the other hand, we developed several transgenic-knockout mouse lines expressing distinct peptides as a single species. By comparing T cell differentiation among these mice, we found positive selection is both specific and degenerate, dependending on the amino acid residues at TCR contacts of the selecting self-peptides.

尽管通过5个基因片段的随机重排和随机核苷酸加成，理论上T细胞受体(αβT cell Receptor，TCR)的多样性达到10；15和15，但成熟T细胞表达高度选择性的TCR，因为它们对自身抗原肽和自身MHC分子的限制表现出耐受性。这主要是由于胸腺T细胞发育过程中处于CD4^+CD8^+阶段的两个相互选择过程，即正向选择和负向选择。利用针对CD4~+CD8~+胸腺细胞的单抗，我们发现缺乏TCR-MHC/肽复合体相互作用的CD_4~+CD8~+胸腺细胞特异性地表达多聚体Thy1分子。另一方面，我们发展了几个表达不同多肽的转基因敲除小鼠品系作为一个单一物种。通过比较这些小鼠的T细胞分化，我们发现，正向选择既是特异性的，也是简并的，取决于选择的自体肽TCR接触处的氨基酸残基。

项目成果

Sano, T., Yamamoto, K., Fukui, Y., Sasazuki, T.: "Spontaneous clustering of Thy-1 antigens on CD4^+CD8^+ thymocytes lacking TCR engagement by MHC/peptide complexes."Eur.J.Immunol.. 29 (2). 403-412 (1999)

Sano, T.、Yamamoto, K.、Fukui, Y.、Sasazuki, T.：“Thy-1 抗原在 CD4^ CD8^ 胸腺细胞上自发聚集，缺乏 MHC/肽复合物的 TCR 参与。”Eur.J.Immunol。

Fukui, Y., Oono, T., Cabaniols, J.P., Nakao, K., Hirokawa, K., Inayoshi, A., Sanui, T., Kanellopoulos, J., Iwata, E., Noda, M., Katsuki, M., Kourilsky, P., Sasazuki, T.: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affec

Fukui, Y.、Oono, T.、Cabaniols, J.P.、Nakao, K.、Hirokawa, K.、Inayoshi, A.、Sanui, T.、Kanellopoulos, J.、Iwata, E.、Noda, M.、Katsuki

Nishimura H, Washizu J, Naiki Y, Hara T, Fukui Y, Sasazuki T, Yoshikai Y.: "MHC class II-dependent NK1.1+γδ T cells are induced in mice by Salmonella infection."J.Immunol.. 162 (3). 1573-1581 (1999)

Nishimura H、Washizu J、Naiki Y、Hara T、Fukui Y、Sasazuki T、Yoshikai Y.：“沙门氏菌感染在小鼠中诱导 MHC II 类依赖性 NK1.1+γδ T 细胞。”J.Immunol.. 162 （3）。1573-1581（1999）。

Matsuki N: "Prevention of infection of influenza virus in DQ6 mice, a human model, by a peptide vaccine prepared according to the cassette theory."Vaccine. 17. 1161-1168 (1999)

Matsuki N：“通过根据盒式理论制备的肽疫苗预防人类模型 DQ6 小鼠中流感病毒的感染。”疫苗。

Sano T: "Spontaneous clustering of Thy-1 antigens on CD4^+CD8^+ thymocytes lacking TCR engagement by MHC/peptide complex."Eur.J.Immunol.. 29. 403-412 (1999)

Sano T：“Thy-1 抗原在缺乏 MHC/肽复合物参与的 TCR 参与的 CD4^ CD8^ 胸腺细胞上自发聚集。”Eur.J.Immunol.. 29. 403-412 (1999)