对T细胞受体克隆型肽类的免疫应答(英文)

Immune response to TCR clonotypic peptides *

目的：皮肤Ｔ细胞淋巴瘤（ＣＴＣＬ）是记忆性诱导Ｔ细胞肿瘤，表达独特的Ｔ细胞受体（ＴＣＲ）的α和β链，两者各含有克隆性独特蛋白序列。这些序列由独特型或第３决定簇互补区（ＣＤＲ３）组成。理论上，来源于ＴＣＲＣＤＲ３的肽类可作为由主要组织相容性复合体（ＭＨＣ）Ⅰ类分子提呈的肿瘤特异抗原。本研究旨在确定细胞毒性Ｔ淋巴细胞（ＣＴＬ）是否识别ＣＤＲ３来源的肽类。方法：首先培育出能裂解２例ＣＴＣＬ病人自身的肿瘤细胞的ＣＴＬ（ＣＤ８＋）细胞株，然后检测这些ＣＴＬ对由原始Ｂ淋巴细胞提呈的源于自身恶性细胞ＴＣＲＣＤＲ３序列的合成肽产生应答的能力。结果：ＣＴＬ分泌肿瘤坏死因子（ＴＮＦα），对自身ＴＣＲβ链独特型肽产生应答，但对来源于其他ＴＣＲβ链独特型区的肽或对照肽不产生应答。抗ＭＨＣⅠ类分子的单克隆抗体（Ｗ６／３２）能阻断其肽的识别。结论：首先表明ＣＴＬ可识别具有ＣＴＣＬ病人个体独特性的恶性淋巴细胞克隆的特异ＭＨＣⅠ类分子相关肽并对其产生应答；又提示起刺激作用的肽来源于ＴＣＲβ链独特型区。该研究建立了这种机制，其他Ｔ细胞可通过此机制调解既定的抗原特异性Ｔ细胞。ＣＴＣＬ的肿瘤特异性表位的鉴定，可能有助开发强化或启动ＣＤ８介导的?

Aim: To determine whether cytotoxic T lymphocytes (CTL) recognize CDR3 derived peptides.Cutaneous T cell lymphoma (CTCL) is a T cell neoplasm of inducer memory T cells that express unique clonal T cell receptors (TCR) α and β chains,each of which contain clonally unique protein sequences.These sequences comprise the idiotypic or third complementarity determining regions (CDR3).Peptides derived from the TCR CDR3 could theoretically serve as tumor specific antigens presented by class Ⅰ major histocompatibility (MHC) molecules.Methods: We first developed cytotoxic CD8 + T cell lines that had autolysis of malignant cells from 2 patients with CTCL,and then tested the ability of these cytotoxic cells to respond to B lymphoblasts presenting synthetic peptides derived from the TCR CDR3 sequences of autologous malignant cells.Results: The cytotoxic T cells secreted TNF α in response to autologous TCR β chain idiotypic peptides,but did not respond to peptides derived from other TCR β chain idiotypic regions,or to other control peptides.Peptide recognition was blocked by an anti class Ⅰ MHC monoclonal antibody,W6/32.Conclusions: This is the first demonstration that CTL may recognize and respond to a specific MHC class Ⅰ associated peptide unique to individual malignant clones of lymphocytes in CTCL.Because the stimulating peptides are derived from the idiotypic region of the TCR β chain,there may be a mechanism by which T cells of a given antigen specificty can be regulated by other T cells.The identification of a tumor specific epitope in this disease may permit the development of vaccines that boost or initiate the CD8 mediated immune response to the tumor cells.