Review

Immunogenetics

, Volume 64, Issue 2, pp 77-85

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • L. J. D’OrsognaAffiliated withDepartment of Immunohematology and Blood Transfusion, Leiden University Medical CentreUniversity of Western AustraliaPathWest Laboratory Medicine Email author 
  • , D. L. RoelenAffiliated withDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Centre
  • , I. I. N. DoxiadisAffiliated withDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Centre
  • , F. H. J. ClaasAffiliated withDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Centre

Abstract

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.

Keywords

Allorecognition Memory T cells Antiviral immunity Heterologous immunity Tissue specificity Alloantibodies