Advances in Direct T-Cell Alloreactivity: Function, Avidity, Biophysics and Structure

Authors

  • C. Smith,

    1. Australian Centre for Vaccine Development, Tumour Immunology Laboratory and Cellular Immunology Laboratory, Queensland Institute of Medical Research, Herston, Brisbane, Australia
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    • Both the authors have contributed equally to this work and their order should be considered arbitrary.

  • J. J. Miles,

    1. Australian Centre for Vaccine Development, Tumour Immunology Laboratory and Cellular Immunology Laboratory, Queensland Institute of Medical Research, Herston, Brisbane, Australia
    2. Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom
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    • Both the authors have contributed equally to this work and their order should be considered arbitrary.

  • R. Khanna

    Corresponding author
    1. Australian Centre for Vaccine Development, Tumour Immunology Laboratory and Cellular Immunology Laboratory, Queensland Institute of Medical Research, Herston, Brisbane, Australia
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Rajiv Khanna, rajiv.khanna@qimr.edu.au

Abstract

Although T-cell-based adaptive immunity plays a crucial role in protection against infectious pathogens and uncontrolled outgrowth of malignant cells, a large portion of these T cells are also capable of responding to allogeneic HLA molecules, violating the paradigm of self-major histocompatibility complex (MHC) restriction. Recent studies have provided insights into the mechanisms by which these T cells recognize allogeneic targets. The role of antiviral T cells in direct alloreactivity through peptide-dependent molecular mimicry and alternate peptide-MHC docking modes has emerged as major models for the human alloresponse. Here, we review in depth recent advances in this field and discuss how molecular interactions between T cells and HLA molecules drive the activation of these effector cells and its potential implications for alloreactivity in human transplantation.

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