正常人與癌症病人的T細胞接受器基因表現之研究

Abstract

T細胞在免疫反應中扮演相當重要的角色，例如殺死被感染的細胞，參與發炎反應的控制，以及協助B細胞製造抗體等功能。T細胞辨識抗原的方式是利用細胞表面的T細胞接受器與抗原呈現細胞上的主要組織相容性複體以及一段經過處理的抗原結合而成。由實驗及臨床上的研究結果顯示，滲透入腫瘤組織的T細胞被認為是腫瘤病人的免疫系統所產生的一種局部對抗腫瘤的反應。我們利用分子生物的技術，針對T細胞接受器α與δ基因去研究其在正常人及癌症病人中的表現性質與基因使用情形。我們發現到在Vα-Cδ或 Vδ-Cα的組合之中，可以確定這類不尋常的重組在RNA level上是可以發生的，而且某些基因的使用情形的確較高。在分析TILs中的基因表現上，發現某些V-D-J 接合區域的基因順序是固定的，但在分析PBLs時此現象則不存在。此外，我們還發現了新的Jδ基因。接下來我們將會針對更多的腫瘤內TILs 去分析其TCR基因的表現性質，希望能藉此瞭解T細胞針對腫瘤所產生的反應機制。

The T cell antigen receptor (TCR) recognizes antigens in the form of short peptides bound to a major histocompatibility complex (MHC) molecule. Based on experimental and clinical data, it appears that human T cells are capable of mediating tumor cell destruction and are potentially important for immunotherapy of cancer. Our objective is to characterize the molecular structure of the TCR genes expressed by tumor-infiltrating lymphocytes (TILs) of patients with cancer. Here we focused on the expression of TCRαand δgenes. First, we identified transcribed TCR genes in lymphocytes isolated from lymphoid organs, such as spleen and thymus, of normal person. Second, we analysed transcribed TCR genes in peripheral blood lymphocytes (PBLs) and TILs, and compared the V,D and J gene usage and the V-(D)-J junxpressed in PBLs and TILs from patients with those of normal persons. We verified that the recombination of Vα-Cδ or Vδ-Cα did occur, and we found that there are some identical sequences at the junction region of TCR on TILs. In addition, a new Jδ gene segment was discovered.