Preferential HLA-B27 Allorecognition Displayed by Multiple Cross-Reactive Antiviral CD8+ T Cell Receptors

Frontiers in Immunology, vol. 11, pp. 248

Abstract

T cells provide essential immunosurveillance to combat and eliminate infection from pathogens, yet these cells can also induce unwanted immune responses via T cell receptor (TCR) cross-reactivity, also known as heterologous immunity. Indeed, pathogen-induced TCR cross-reactivity has shown to be a common, robust and functionally potent mechanism that can trigger a spectrum of human immunopathologies associated with either transplant rejection, drug allergy and autoimmunity. Here, we report that several virus-specific CD8+ T cells directed against peptides derived from chronic viruses (EBV, CMV and HIV-1) presented by high frequency HLA-A and -B allomorphs differentially cross-react towards HLA-B27 allotypes in a highly focused and hierarchical manner. Given the commonality of cross-reactive T cells and their potential contribution to adverse outcomes in allogeneic transplants our study demonstrates that multiple antiviral T cells recognizing the same HLA allomorph could pose an extra layer of complexity for organ matching.

Authors 10

1. Louise C. Rowntree

   The Alfred Hospital · Monash University

   Affiliation as printed

   Department of Allergy, Immunology, and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia

   Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

   Respiratory Medicine Laboratory, Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC, Australia

2. Heleen van den Heuvel Aachen Department of Immunohaematology and Blood Transfusion

   Leiden University Medical Center · Monash University

   Affiliation as printed

   Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands

   Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

3. Jessica D. Sun

   Monash University

   Affiliation as printed

   Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

4. Lloyd J. A. D'Orsogna

   The University of Western Australia · Fiona Stanley Hospital

   Affiliation as printed

   Department of Clinical Immunology and Pathwest, Fiona Stanley Hospital, Perth, WA, Australia

   School of Medicine, University of Western Australia, Perth, WA, Australia

5. Thi H. O. Nguyen

   The University of Melbourne · Peter Doherty Institute

   Affiliation as printed

   Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia

6. Frans H.J. Claas Aachen Department of Immunohaematology and Blood Transfusion

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands

7. Jamie Rossjohn

   Monash University · Cardiff University

   Affiliation as printed

   Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia

   Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

   Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom

8. Tom C. Kotsimbos

   The Alfred Hospital · Monash University

   Affiliation as printed

   Department of Allergy, Immunology, and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia

   Respiratory Medicine Laboratory, Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC, Australia

9. Anthony Wayne Purcell

   Monash University

   Affiliation as printed

   Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

10. Nicole A. Mifsud corresponding

    The Alfred Hospital · Monash University

    Affiliation as printed

    Department of Allergy, Immunology, and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia

    Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

    Respiratory Medicine Laboratory, Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC, Australia