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Immunogenetics. 2012 Feb;64(2):77-85. doi: 10.1007/s00251-011-0590-0. Epub 2011 Dec 3.

TCR cross-reactivity and allorecognition: new insights into the immunogenetics of allorecognition.

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Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, PO Box 9600, 2300RC Leiden, the Netherlands.


Alloreactive T cells are core mediators of graft rejection and are a potent barrier to transplantation tolerance. It was previously unclear how T cells educated in the recipient thymus could recognize allogeneic HLA molecules. Recently it was shown that both naïve and memory CD4+ and CD8+ T cells are frequently cross-reactive against allogeneic HLA molecules and that this allorecognition exhibits exquisite peptide and HLA specificity and is dependent on both public and private specificities of the T cell receptor. In this review we highlight new insights gained into the immunogenetics of allorecognition, with particular emphasis on how viral infection and vaccination may specifically activate allo-HLA reactive T cells. We also briefly discuss the potential for virus-specific T cell infusions to produce GvHD. The progress made in understanding the molecular basis of allograft rejection will hopefully be translated into improved allograft function and/or survival, and eventually tolerance induction.

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