Gojanovich Greg S, Hess Paul R
Department of Clinical Sciences and Immunology Program, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA.
Clin Dev Immunol. 2012;2012:380289. doi: 10.1155/2012/380289. Epub 2012 May 28.
Classical major histocompatibility complex (MHC) class I and II molecules present peptides to cognate T-cell receptors on the surface of T lymphocytes. The specificity with which T cells recognize peptide-MHC (pMHC) complexes has allowed for the utilization of recombinant, multimeric pMHC ligands for the study of minute antigen-specific T-cell populations. In type 1 diabetes (T1D), CD8+ cytotoxic T lymphocytes, in conjunction with CD4+ T helper cells, destroy the insulin-producing β cells within the pancreatic islets of Langerhans. Due to the importance of T cells in the progression of T1D, the ability to monitor and therapeutically target diabetogenic clonotypes of T cells provides a critical tool that could result in the amelioration of the disease. By administering pMHC multimers coupled to fluorophores, nanoparticles, or toxic moieties, researchers have demonstrated the ability to enumerate, track, and delete diabetogenic T-cell clonotypes that are, at least in part, responsible for insulitis; some studies even delay or prevent diabetes onset in the murine model of T1D. This paper will provide a brief overview of pMHC multimer usage in defining the role T-cell subsets play in T1D etiology and the therapeutic potential of pMHC for antigen-specific identification and modulation of diabetogenic T cells.
经典的主要组织相容性复合体（MHC）I类和II类分子将肽段呈递给T淋巴细胞表面的同源T细胞受体。T细胞识别肽-MHC（pMHC）复合物的特异性使得重组多聚体pMHC配体可用于研究微量抗原特异性T细胞群体。在1型糖尿病（T1D）中，CD8 + 细胞毒性T淋巴细胞与CD4 + T辅助细胞共同作用，破坏胰岛内产生胰岛素的β细胞。由于T细胞在T1D进展中的重要性，监测和治疗性靶向致糖尿病T细胞克隆型的能力提供了一种关键工具，可能会改善该疾病。通过给予与荧光团、纳米颗粒或毒性部分偶联的pMHC多聚体，研究人员已经证明能够枚举、追踪和清除至少部分导致胰岛炎的致糖尿病T细胞克隆型；一些研究甚至在T1D小鼠模型中延迟或预防糖尿病的发生。本文将简要概述pMHC多聚体在确定T细胞亚群在T1D病因学中的作用以及pMHC在抗原特异性识别和调节致糖尿病T细胞方面的治疗潜力方面的应用。
