title: TCR cross-reactivity and allorecognition: new insights into the immunogenetics of allorecognition.
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.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, PO Box 9600, 2300RC Leiden, the Netherlands. lloyd.dorsogna@health.wa.gov.au
authors.forename: L J
authors.initials: LJ
authors.lastname: D'Orsogna
authors.forename: D L
authors.initials: DL
authors.lastname: Roelen
authors.forename: I I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D007518:Isoantibodies / Q000235:genetics / Q000276:immunology; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014184:Transplantation, Homologous; D014777:Virus Diseases / Q000276:immunology
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell