title: Deciphering the clinical relevance of allo-human leukocyte antigen cross-reactivity in mediating alloimmunity following transplantation.
abstract: OBJECTIVE
  Despite a growing awareness regarding the potential of cross-reactive virus-specific memory T cells to mediate alloimmunity, there has been limited clinical evaluation on allograft immunopathology. This review will explore published models of human T-cell cross-reactivity and discuss criteria required to drive this mechanism as a contributing cause of allograft dysfunction in transplantation.
  
  
  RESULTS
  Published models of human allogeneic (allo)-human leukocyte antigen (HLA) cross-reactivity have enabled dissection of the cross-reactive T cell receptor/peptide/major histocompatibility complex (TCR/peptide/MHC) interaction. In many of the models, the cross-reactive T cells express a unique TCR, although the relevance of a public cross-reactive TCR repertoire has yet to be determined. Equally, allopeptide identity, a vital component driving cross-recognition, remains unknown in the majority of models thereby prompting further characterization utilizing novel technologies. Although clinical studies examining the presence and impact of specific cross-reactive virus-specific T cells have been minimally explored, the existing data suggest that there may be a marginal set of requirements that need to be satisfied before the potentially damaging effects of allo-HLA cross-reactivity can be realized.
  
  
  CONCLUSIONS
  Our understanding of allo-HLA cross-reactivity continues to evolve as improved technology and novel strategies allow us to better question the contribution of allo-HLA cross-reactivity in clinically relevant allograft dysfunction.
authors.affiliation: aDepartment of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne bInfection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton cDepartment of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville dAustralian Research Council Centre of Excellence for Advanced Molecular Imaging eDepartment of Medicine, Central Clinical School, Monash University, Clayton, VIC, Australia.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Rowntree
authors.forename: Thi H O
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Tom C
authors.initials: TC
authors.lastname: Kotsimbos
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mifsud
mesh_terms: D000818:Animals; D015551:Autoimmunity; D003429:Cross Reactions; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens