Heemskerk Martin B A, Roelen Dave L, Dankers Marlies K A, van Rood Jon J, Claas Frans H J, Doxiadis Ilias I N, Oudshoorn Machteld
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Hum Immunol. 2005 Sep;66(9):969-76. doi: 10.1016/j.humimm.2005.06.007. Epub 2005 Oct 10.
CD8+ T cell-mediated alloreactivity is generally believed to involve recognition of the alpha1/alpha2 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.
一般认为，CD8 + T细胞介导的同种异体反应性涉及对供体I类MHC分子的α1/α2结构域及其所结合肽段的识别。以细胞毒性T淋巴细胞前体（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对造血干细胞供体/受者，这些供体/受者在单个HLA - A、- B和 - C位点存在一系列等位基因差异，旨在探究此类错配的预测价值。与等位基因差异程度越大将导致更多同种异体反应性的预期相反，我们发现，在大量病例中，具有众多序列差异的I类MHC分子并未引发同种异体CTL反应。我们提出，在产生对自身MHC反应性足够狭窄的T细胞库时，阳性胸腺选择限制了识别结构和序列已广泛分化的同种异体MHC分子的能力。这些发现对于供体和受者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。
