Allogeneic MHC class I molecules with numerous sequence differences do not elicit a CTL response
Allogeneic MHC class I molecules with numerous sequence differences do not elicit a CTL response
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DOI：
10.1016/j.humimm.2005.06.007
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发表时间：
2005-09-01
期刊：
影响因子：
2.7
通讯作者：
Oudshoorn, M
中科院分区：
文献类型：
--
作者：
Heemskerk, MBA;Roelen, DL;Oudshoorn, M
CD8+ T细胞介导的同种异体反应通常被认为涉及对供体型I类MHC分子的α 1/ α 2结构域及其结合的肽的识别。使用CTLp检测结果作为诱导同种异体反应性的参数，我们回顾性调查了80对造血干细胞供者/患者，这些造血干细胞在单个HLA-A、-B和-C位点上具有一系列等位基因差异，试图探索这种不匹配的预测价值。与预期更大程度的等位基因差异会导致更多的同种异体反应性相反，我们发现在相当数量的情况下，具有大量序列差异的I类MHC分子不会引起同种异体CTL反应。我们提出，在产生对自身MHC反应足够窄的T细胞库时，胸腺阳性选择限制了识别结构和序列差异很大的同种异体MHC分子的能力。这些发现对于供体和患者MHC匹配策略以及我们对造血干细胞移植后T细胞-MHC相互作用的理解具有重要意义。人类免疫学66,969-976（2005）。(c)美国组织相容性和免疫遗传学学会，2005年。Elsevier Inc.出版。
CD8+ T cell-mediated alloreactivity is generally believed to involve recognition of the alpha 1/alpha 2 domains of donor-type class I MHC molecules as well as the peptides they bind. Using the CTLp assay outcome as a parameter for the induction of alloreactivity, we have retrospectively surveyed 80 haematopoietic stem cell donor/patient pairs that feature a range of allelic differences at single HLA-A, -B, and -C loci in an attempt to probe the predictive value of such mismatches. In contrast to the expectation that greater degree of allelic disparity would lead to more alloreactivity, we found that in a substantial number of cases, class I MHC molecules with numerous sequence differences did not elicit an allogeneic CTL response. We propose that in generating a T cell repertoire with a sufficiently narrow responsive for self-MHC, positive thymic selection limits the capacity to recognize allogeneic MHC molecules whose structure and sequence have diverged extensively. These findings are important for donor and patient MHC matching strategies and our understanding of T cell-MHC interaction after haematopoietic stem cell transplantation. Human Immunology 66, 969-976 (2005). (c) American Society for Histocompatibility and Immunogenetics, 2005. Published by Elsevier Inc.