Legge K L, Min B, Cestra A E, Pack C D, Zaghouani H
Department of Microbiology, University of Tennessee, Knoxville 37996, USA.
J Immunol. 1998 Jul 1;161(1):106-11.
Ig-PLP1 and Ig-PLP-LR are chimeric Igs expressing proteolipid protein (PLP)-derived T cell agonist (PLP1) and antagonist (PLP-LR) peptides, respectively. Both chimeras, like free PLP1 and PLP-LR peptides, induce in vivo-specific T cell responses. However, the responses induced by Ig-PLP1 and Ig-PLP-LR were cross-reactive with both PLP1 and PLP-LR peptides, while those induced by free peptides were not. Surprisingly, despite the cross-reactivity of the responses, when Ig-PLP1 and Ig-PLP-LR were administered together into mice, a dose-dependent down-regulation of both T cell responses and a reduction of IL-2 production to background levels was observed. In contrast, when T cells induced by either Ig chimera were stimulated in vitro with mixtures of free PLP1 and PLP-LR peptides, there was no down-regulation of proliferation or decrease in IL-2 production. These data indicate that Ig-PLP1 and Ig-PLP-LR exert adverse reactions on one another at the level of naive T cells, resulting in an opposite antagonism. However, naive T cells experiencing either chimera develop into cross-reactive cells, acquire resistance to TCR triggering by closely related but different peptides, and support responsiveness.
Ig-PLP1和Ig-PLP-LR是嵌合免疫球蛋白，分别表达来源于蛋白脂蛋白（PLP）的T细胞激动剂（PLP1）和拮抗剂（PLP-LR）肽段。这两种嵌合体，与游离的PLP1和PLP-LR肽段一样，在体内诱导特异性T细胞反应。然而，Ig-PLP1和Ig-PLP-LR诱导的反应与PLP1和PLP-LR肽段都具有交叉反应性，而游离肽段诱导的反应则没有。令人惊讶的是，尽管反应具有交叉反应性，但当将Ig-PLP1和Ig-PLP-LR一起注射到小鼠体内时，观察到T细胞反应呈剂量依赖性下调，且白细胞介素-2的产生减少至背景水平。相反，当用游离的PLP1和PLP-LR肽段混合物在体外刺激由任一Ig嵌合体诱导的T细胞时，增殖没有下调，白细胞介素-2的产生也没有减少。这些数据表明，Ig-PLP1和Ig-PLP-LR在初始T细胞水平上相互产生不良反应，导致相反的拮抗作用。然而，接触任一嵌合体的初始T细胞会发育成交叉反应性细胞，获得对密切相关但不同肽段触发TCR的抗性，并支持反应性。
