Altered ligands reveal limited plasticity in the T cell response to a pathogenic epitope.
Altered ligands reveal limited plasticity in the T cell response to a pathogenic epitope.
复制标题
法配体的改变揭示了T细胞对病原表位的响应中的可塑性有限。
DOI：
10.1084/jem.189.7.1111
复制
发表时间：
1999-04-05
影响因子：
15.3
通讯作者：
Locksley, R M
中科院分区：
文献类型：
--
作者：
Pingel, S;Launois, P;Fowell, D J;Turck, C W;Southwood, S;Sette, A;Glaichenhaus, N;Louis, J A;Locksley, R M
实验性利什曼病为辅助性T细胞1型（Th1）介导的细胞内病原体感染控制提供了一个特征明确的模型。易感的BALB/c小鼠在感染后异常地产生Th2细胞，无法控制寄生虫的传播。这些小鼠早期的CD4 + T细胞反应是寡克隆性的，反映了携带Vβ4/Vα8的T细胞针对来自哺乳动物受体活化蛋白激酶C1（RACK1）的利什曼原虫同源物（LACK）抗原的单个表位的扩增。这些细胞产生的白细胞介素4（IL - 4）被认为引导了后续的Th2反应。我们使用来自表达这种Vβ4/Vα8受体的T细胞受体转基因小鼠的T细胞来表征对I - Ad具有相似亲和力的变异肽配体。这种变异配体无法激活转基因LACK特异性T细胞产生IL - 4，也无法在注射到BALB/c小鼠体内后激活。用变异肽配体对易感小鼠进行预处理显著改变了后续感染的进程。使用仅一个氨基酸不同的变异肽就能使原本易感的小鼠获得自愈表型的能力表明，识别这种抗原的内源性T细胞库多样性有限。
Experimental leishmaniasis offers a well characterized model of T helper type 1 cell (Th1)-mediated control of infection by an intracellular organism. Susceptible BALB/c mice aberrantly develop Th2 cells in response to infection and are unable to control parasite dissemination. The early CD4+ T cell response in these mice is oligoclonal and reflects the expansion of Vβ4/ Vα8-bearing T cells in response to a single epitope from the parasite Leishmania homologue of mammalian RACK1 (LACK) antigen. Interleukin 4 (IL-4) generated by these cells is believed to direct the subsequent Th2 response. We used T cells from T cell receptor–transgenic mice expressing such a Vβ4/Vα8 receptor to characterize altered peptide ligands with similar affinity for I-Ad. Such altered ligands failed to activate IL-4 production from transgenic LACK-specific T cells or following injection into BALB/c mice. Pretreatment of susceptible mice with altered peptide ligands substantially altered the course of subsequent infection. The ability to confer a healer phenotype on otherwise susceptible mice using altered peptides that differed by a single amino acid suggests limited diversity in the endogenous T cell repertoire recognizing this antigen.