Mechanisms of indirect allorecognition: characterization of MHC class II allopeptide-specific T helper cell clones from animals undergoing acute allograft rejection.
Mechanisms of indirect allorecognition: characterization of MHC class II allopeptide-specific T helper cell clones from animals undergoing acute allograft rejection.
复制标题
间接同种异体识别机制：来自经历急性同种异体移植排斥的动物的 MHC II 类同种肽特异性 T 辅助细胞克隆的表征。
DOI：
10.1097/00007890-199804150-00004
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发表时间：
1998
期刊：
影响因子：
6.2
通讯作者：
Sayegh,MH
中科院分区：
文献类型：
--
作者：
Waaga,AM;Chandraker,A;Spadafora-Ferreira,M;Iyengar,AR;Khoury,SJ;Carpenter,CB;Sayegh,MH
背景：最近的证据表明，通过同种异体识别的间接途径激活的T细胞在同种异体移植排斥反应中起重要作用，尽管其效应机制尚不清楚。本研究的目的是表征和研究的体内功能的自限制性MHC同种异体肽特异性T细胞克隆产生的动物经历allograft rejection.Methods和Results.We产生的自限制性II类MHC同种异体肽特异性T细胞克隆脾和肾的刘易斯（LEW; RT 1 1）大鼠进行急性排斥反应的MHC不相容的Wistar Furth（WF; RT 1 u）肾同种异体移植。RT1。来自排斥动物脾脏和肾脏的D u β20-44肽特异性CD 4 + T辅助细胞1克隆表达限制性T细胞受体（TCR）Vβ库：Vβ4、8.2或9。相比之下，从RT 1产生的克隆。D u β20-44免疫LEW大鼠均表达TCR Vβ9。RT 1的氨基酸序列。D 1（LEW）和RT 1。D u（WF）残基20-44仅在位置30和38处不同。表达TCR Vβ9的T细胞克隆优先增殖为肽片段RT 1。D u β20-33。表达TCR Vβ4的T细胞克隆微弱地增殖为肽片段RT 1。D u β20-33和31-44，而表达TCR Vβ8的那些。2优先于肽片段31-44增殖。表达TCR Vβ9或Vβ8的T细胞克隆的连续转移。2，但不是Vβ4，幼稚LEW动物引起显着的迟发型超敏反应后，挑战与RT 1。结论：这是首次报道急性排斥反应动物自体限制性MHC同种异型肽特异性T细胞克隆的细胞、分子和功能特征。我们的数据为间接同种异体识别在同种异体移植排斥反应中的生物学重要作用提供了支持。
Background.Recent evidence indicates that T cells primed via the indirect pathway of allorecognition play an important role in allograft rejection, although the effector mechanisms remain unknown. The purpose of this study was to characterize and study the in vivo function of self-restricted MHC allopeptide-specific T-cell clones generated from animals undergoing allograft rejection.Methods and Results.We generated self-restricted class II MHC allopeptide-specific T-cell clones from the spleen and kidney of Lewis (LEW; RT1 1) rats undergoing acute rejection of MHC-incompatible Wistar Furth (WF; RT1 u) renal allografts. RT1. D u β20-44 peptide-specific CD4+ T helper 1 clones from the spleen and kidney of rejecting animals expressed a restricted T cell receptor (TCR) Vβ repertoire: Vβ4, 8.2, or 9. In comparison, clones generated from RT1. D u β20-44 immunized LEW rats all expressed TCR Vβ9. The amino acid sequence of RT1. D 1 (LEW) and RT1. D u (WF) residues 20-44 differ only at positions 30 and 38. T-cell clones expressing TCR Vβ9 preferentially proliferated to the peptide fragment RT1. D u β20-33. T-cell clones expressing TCR Vβ4 proliferated weakly to peptide fragments RT1. D u β20-33 and 31-44, whereas those expressing TCR Vβ8. 2 proliferated preferentially to the peptide fragment 31-44. Adoptive transfer of T-cell clones expressing TCR Vβ9 or Vβ8. 2, but not Vβ4, to naive LEW animals elicited significant delayed-type hypersensitivity responses after challenge with the RT1. D u β20-44 peptide or allogeneic WF (RT1 u) splenocytes.Conclusion.This is the first report on the cellular, molecular, and functional characterization of self-restricted MHC allopeptide-specific T-cell clones from animals undergoing acute rejection. Our data provide support for a biologically significant role of indirect allorecognition in allograft rejection.