title: What Is Direct Allorecognition?
abstract: Direct allorecognition is the process by which donor-derived major histocompatibility complex (MHC)-peptide complexes, typically presented by donor-derived 'passenger' dendritic cells, are recognised directly by recipient T cells. In this review, we discuss the two principle theories which have been proposed to explain why individuals possess a high-precursor frequency of T cells with direct allospecificity and how self-restricted T cells recognise allogeneic MHC-peptide complexes. These theories, both of which are supported by functional and structural data, suggest that T cells recognising allogeneic MHC-peptide complexes focus either on the allopeptides bound to the allo-MHC molecules or the allo-MHC molecules themselves. We discuss how direct alloimmune responses may be sustained long term, the consequences of this for graft outcome and highlight novel strategies which are currently being investigated as a potential means of reducing rejection mediated through this pathway.
authors.affiliation: MRC Centre for Transplantation, King's College London, Guy's Hospital, London, SE1 9RT UK ; NIHR Biomedical Research Centre, Guy's & St Thomas' NHS Foundation Trust & King's College London, Guy's Hospital, London, SE1 9RT UK.
authors.forename: Dominic A
authors.initials: DA
authors.lastname: Boardman
authors.affiliation: MRC Centre for Transplantation, King's College London, Guy's Hospital, London, SE1 9RT UK.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Jacob
authors.affiliation: MRC Centre for Transplantation, King's College London, Guy's Hospital, London, SE1 9RT UK ; School of Health, Sport and Bioscience, Stratford Campus, University of East London, London, E15 4LZ UK.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Smyth
authors.affiliation: MRC Centre for Transplantation, King's College London, Guy's Hospital, London, SE1 9RT UK ; NIHR Biomedical Research Centre, Guy's & St Thomas' NHS Foundation Trust & King's College London, Guy's Hospital, London, SE1 9RT UK.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: MRC Centre for Transplantation, King's College London, Guy's Hospital, London, SE1 9RT UK ; NIHR Biomedical Research Centre, Guy's & St Thomas' NHS Foundation Trust & King's College London, Guy's Hospital, London, SE1 9RT UK.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
keywords: Allorecognition; Allospecificity; High determinant density; Multiple binary complexes; Transplantation