Endogenous-peptide-dependent alloreactivity: new scientific insights and clinical implications

Lloyd J D'Orsogna, Thi Hoang Oanh Nguyen, Frans HJ Claas, Campbell S Witt, Nicole Andrea Mifsud

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13 Citations (Scopus)


T-cell alloreactivity is generated via immune responsiveness directed against allogeneic (allo) human leucocyte antigen (HLA) molecules. Whilst the alloresponse is of extraordinary potency and frequency, it has often been assumed to be less peptide-specific than conventional T-cell reactivity. Recently, several human studies have shown that both alloreactive CD8+ and CD4+ T cells exhibit exquisite allo-HLA and endogenous peptide specificity that has also underpinned tissue-specific allorecognition. In this review, we summarize former and recent scientific evidence in support of endogenous peptide (self-peptide)-dependence of T-cell alloreactivity. The clinical implications of these findings will be discussed in the context of both solid organ transplantation and haematopoietic stem cell transplantation (HSCT). Insights into the understanding of the molecular basis of T-cell allorecognition will probably translate into improved allograft survival outcomes, lower frequencies of graft vs host disease and could potentially be exploited for selective graft vs leukaemia effect to improve clinical outcomes following HSCT.
Original languageEnglish
Pages (from-to)399 - 407
Number of pages9
JournalTissue Antigens
Issue number6
Publication statusPublished - 2013

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