ROLE OF ENDOGENOUS PEPTIDE IN HUMAN ALLOREACTIVE CYTOTOXIC T-CELL RESPONSES
ROLE OF ENDOGENOUS PEPTIDE IN HUMAN ALLOREACTIVE CYTOTOXIC T-CELL RESPONSES
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DOI：
10.1093/intimm/4.3.367
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发表时间：
1992-03-01
影响因子：
4.4
通讯作者：
ENGELHARD, VH
中科院分区：
文献类型：
--
作者：
MAN, S;SALTER, RD;ENGELHARD, VH
T x B杂交体174 x CEM. T2（T2）已被证明在由MHC I类分子呈递的蛋白质加工中有缺陷。然而，它继续表达显著量的HLA-A2.1，表明这种I类分子以基本上无肽的形式或与肽的小子集结合表达。在本文中，T2与有限稀释分析结合使用，以提供对同种异体反应性细胞毒性T淋巴细胞（CTL）的分数的直接估计，所述CTL依赖于肽的存在来识别HLA-A2.1。通过用表达HLA-A2.1的外周血淋巴细胞刺激产生的同种异体反应性细胞毒性T细胞系识别T2较差。对240个克隆有限稀释培养物的裂孔分析表明，这反映了两个亚群的存在。平均85%的HLA-A2.1特异性CTL识别正常细胞上的HLA-A2.1，但不识别T2。其余的人在T2和正常靶点上都能识别HLA-A2.1。以T2为刺激细胞，可产生具有后者特异性的CTL细胞系。使用表达较低密度的HLA-A2.1或表达已突变以影响CD 8结合的HLA-A2分子的靶细胞，未观察到T2反应性和T2非反应性CTL之间的亲合力的显著差异。因此，大多数同种异体反应性CTL识别T2的失败不是该细胞上HLA-A2.1表面表达水平较低的结果，而是由于缺乏适当的表位。这表明HLA-A2.1特异性同种异体反应性CTL识别的大多数表位依赖于T2细胞上不存在或显著减少的内源性肽的存在。这些结果的意义，目前的同种异体反应模型进行了讨论。
The T x B hybrid 174 x CEM.T2 (T2) has been shown to be defective in the processing of proteins for presentation by MHC class I molecules. It continues, however, to express significant quantities of HLA-A2.1, suggesting that this class I molecule is expressed either in a largely peptide-free form or in association with a small subset of peptides. In this paper T2 was used in conjunction with limiting dilution analysis to provide a direct estimate of the fraction of alloreactive cytotoxic T lymphocytes (CTLs) that were dependent upon the presence of peptides for their recognition of HLA-A2.1. Alloreactive cytotoxic T cell lines generated by stimulation with HLA-A2.1 expressing peripheral blood lymphocytes recognized T2 poorly. Split-well analysis of 240 clonal limiting dilution cultures demonstrated that this reflected the existence of two subpopulations. An average 85% of HLA-A2.1 specific CTLs recognized HLA-A2.1 on normal cells but not on T2. The remainder recognized HLA-A2.1 on both T2 and normal targets. CTL lines with the latter specificity could be generated by using T2 as a stimulator cell. Using target cells that either expressed a lower density of HLA-A2.1 or that expressed HLA-A2 molecules that had been mutated to affect CD8 binding, no significant differences in avidity between T2-reactive and T2-unreactive CTLs were seen. Thus the failure of the majority of alloreactive CTLs to recognize T2 is not a consequence of the lower level of HLA-A2.1 surface expression on this cell, but is instead due to the absence of appropriate epitopes. This suggests that most of the epitopes recognized by HLA-A2.1 specific alloreactive CTLs depend upon the presence of endogenous peptides which are absent or significantly reduced on T2 cells. The significance of these results to current models of alloreactivity is discussed.