Role of self-Ia antigen in the recognition of self and not self by T cells: Study by use of cloned T cell lines.

自身 Ia 抗原在 T 细胞识别自身和非自身中的作用：使用克隆 T 细胞系进行研究。

• 批准号: 60480179
• 负责人: SAITO Kazuhisa
• 金额: $ 2.82万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480179/
• 关键词: ABA-tyrosine; Antigen presentation; Antigen recognition by T cell; Auto-A-reactive T cell; Autoimmune disease; Ia-conjugated liposome; Sopped flow method; T細胞の抗原認識; Ia抗原; ABA-tyrosine; propyl-glycine; 自己反応性T細胞クローン; 抗核抗体

1. Even by use of I-A^KK gene-transfected L cells as antigen presenting cells (APC), azobenzenearso- nate-tyrosine (ABA-tyr) specific T cell clones or T hybridomas (I-A^kk restricted) showed increase in DNA synthesis or IL 2 production in respones to ABA-tyr, and these responses were blocked by anti-I-A^KK antibody. 2. To study directly antigen recognition of T cells, we examined changes in Ca^<2+>2 influx and membrane fluidity of T cells after antigen recognition by stopped flow method using fluorescent probes. In the presence of I-A^KK gene-transfected L cells or liposomes conjugated with Ia^KK molecules, ABA-tyr specific T cells showed marked increase in Ca^<2+>2 influx and membrane fluidity within 2 seconds after stimulation with ABA-tyr, and these responses were blocked by anti-I-A^KK antibody. 3. To clarify whether ABA-tyr should bind to Ia molecules before being recognized by T cells, we compared the rate constants of Ca^<2+>2 influx when the order of mixing of T cells, ABA-tyr and APC was changed. The rate constant was almost the same even by change in the order of mixing. These results support the trimolecular complex model of antigen recognition by T cells. 4. Among auto-Ia-reactive T cell clones, noe clone elicited lichen planus-like lesion in the skin of syngeneic mice. Another clone injected i.v. into syngeneic mice caused production of anti-DNA antibody and auto-antibody to erythrocytes. We ate exploring the causes of autoimmune diseases by use of these auto-Ia-reactive T cell clones.

1. 即使使用I-A^KK基因转染的L细胞作为抗原提呈细胞（APC），偶氮苯耳酪氨酸（ABA-tyr）特异性T细胞克隆或T杂交瘤（I-A^ KK限制性）也显示出对ABA-tyr的DNA合成或IL - 2产生增加，而这些反应被抗I-A^KK抗体阻断。2. 为了研究T细胞对抗原的直接识别，我们采用荧光探针停流法检测了抗原识别后T细胞Ca^<2+>2内流和膜流动性的变化。在I-A^KK基因转染的L细胞或与Ia^KK分子结合的脂体存在的情况下，ABA-tyr特异性T细胞在ABA-tyr刺激后2秒内Ca^<2+>2内流和膜流动性明显增加，这些反应被抗I-A^KK抗体阻断。3. 为了弄清ABA-tyr在被T细胞识别之前是否需要与Ia分子结合，我们比较了T细胞、ABA-tyr和APC混合顺序改变时Ca^<2+>2内流的速率常数。即使改变混合顺序，其速率常数也几乎相同。这些结果支持T细胞识别抗原的三分子复合物模型。4. 在自ia反应性T细胞克隆中，没有克隆在同基因小鼠皮肤上引起扁平地衣样病变。另一克隆体注射到同基因小鼠体内，产生抗dna抗体和红细胞自身抗体。我们通过使用这些自身ia反应性T细胞克隆来探索自身免疫性疾病的原因。

项目成果

Kazuhisa Saito et al.: J. Immunol.137. 2485-2495 (1986)

Kazuhisa Saito 等人：J.Immunol.137。

Kazuhisa Saito, et al.: "Cloned auto-Ia-reactive T cells elicit lichen planus-like lesion in the skin of syngeneic mice" J. Immunol.137. 2485-2495 (1986)

Kazuhisa Saito 等人：“克隆的自身 Ia 反应性 T 细胞在同基因小鼠的皮肤中引发扁平苔藓样病变”J.Immunol.137。

Takushi Tadakuma, et al.: "Induction of local GvHR by autoreactive T cell clones maintatined in the presence of syngeneic mouse serum" Proc. Jap. Soc. Immunol.15. 531 (1985)

Takushi Tadakuma 等人：“在同基因小鼠血清存在下维持的自身反应性 T 细胞克隆诱导局部 GvHR”Proc.

Takushi Tadakuma, et al.: "Induction of a syngeneic graft-versus-host reaction in popliteal lymph nodes by cloned autoreactive T cells" J. Immunol.

Takushi Tadakuma 等人：“通过克隆的自身反应性 T 细胞在腘淋巴结中诱导同基因移植物抗宿主反应”J.Immunol。

太田早苗 他: 日本免疫学会総会記録. 15. 314 (1985)

Sanae Ota 等人：日本免疫学会会员大会记录 15. 314 (1985)。