TRIGGERING OF THE T3-TI ANTIGEN RECEPTOR COMPLEX RESULTS IN CLONAL T-CELL PROLIFERATION THROUGH AN INTERLEUKIN 2-DEPENDENT AUTOCRINE PATHWAY
TRIGGERING OF THE T3-TI ANTIGEN RECEPTOR COMPLEX RESULTS IN CLONAL T-CELL PROLIFERATION THROUGH AN INTERLEUKIN 2-DEPENDENT AUTOCRINE PATHWAY
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DOI：
10.1073/pnas.81.5.1509
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
REINHERZ, EL
中科院分区：
文献类型：
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作者：
MEUER, SC;HUSSEY, RE;REINHERZ, EL
利用人T细胞克隆和针对抗原（T3-Ti分子复合物）表面受体的抗T细胞受体抗体（克隆型）以及抗白细胞介素2 （IL-2）和抗IL-2受体抗体，研究同种异体抗原或抗原+自身主要组织相容性复合物（即生理配体）触发特异性克隆增殖的机制。可溶性或sepharose结合的抗ti单克隆抗体，像生理配体一样，通过诱导表面IL-2受体表达增加6倍来增强对纯化IL-2的增殖反应。相比之下，只有sepharose结合的抗ti或生理配体触发内源性克隆IL-2的产生并导致随后的增殖。后者被针对IL-2受体或IL-2本身的抗体阻断。结果表明，在没有T3-Ti受体交联的情况下，诱导IL-2受体表达而不是IL-2释放。抗原诱导的增殖是通过自分泌途径介导的，包括内源性IL-2的产生、释放和随后与IL-2受体的结合。
Human T cell clones and anti-T cell-receptor antibodies (clonotypic) directed at surface receptors for antigen (T3-Ti molecular complex) as well as anti-interleukin 2 (IL-2) and anti-IL-2-receptor antibodies were utilized to investigate the mechanism by which alloantigens or antigen plus self-major histocompatibility complex (i.e., physiologic ligand) trigger specific clonal proliferation. Soluble or Sepharose-bound anti-Ti monoclonal antibodies, like physiologic ligand, enhanced proliferative responses to purified IL-2 by inducing a 6-fold increase in surface IL-2 receptor expression. In contrast, only Sepharose-bound anti-Ti or physiologic ligand triggered endogenous clonal IL-2 production and resulted in subsequent proliferation. The latter was blocked by antibodies directed at either the IL-2 receptor or IL-2 itself. The results suggest that induction of IL-2 receptor expression but not IL-2 release occurs in the absence of T3-Ti receptor cross-linking. Antigen-induced proliferation is mediated through an autocrine pathway involving endogenous IL-2 production, release and subsequent binding to IL-2 receptors.