2. Academic Validation
  3. Divergent paths for the selection of immunodominant epitopes from distinct antigenic sources

Divergent paths for the selection of immunodominant epitopes from distinct antigenic sources

  • Nat Commun. 2014 Nov 21;5:5369. doi: 10.1038/ncomms6369.
AeRyon Kim 1,  Isamu Z Hartman 2,  Brad Poore 1,  Tatiana Boronina 3,  Robert N Cole 3,  Nianbin Song 2,  M Teresa Ciudad 4,  Rachel R Caspi 5,  Dolores Jaraquemada 4,  Scheherazade Sadegh-Nasseri 6
Affiliations

Affiliations

  • 1 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  • 2 The Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  • 3 Department of Biological Chemistry, Mass Spectrometry and Proteomics Facility, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  • 4 Department of Cell Biology, Physiology and Immunology, Laboratori d'Immunologia Cellular, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
  • 5 Laboratory of Immunology, National Eye Institute, NIH, Bethesda, Maryland 20892, USA.
  • 6 1] Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] The Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
PMID: 25413013 DOI: 10.1038/ncomms6369
Abstract

Immunodominant epitopes are few selected epitopes from complex antigens that initiate T-cell responses. Here to provide further insights into this process, we use a reductionist cell-free antigen-processing system composed of defined components. We use the system to characterize steps in antigen processing of pathogen-derived proteins or autoantigens and we find distinct paths for peptide processing and selection. Autoantigen-derived immunodominant epitopes are resistant to digestion by cathepsins, whereas pathogen-derived epitopes are sensitive. Sensitivity to cathepsins enforces capture of pathogen-derived epitopes by major histocompatibility complex class II (MHC class II) before processing, and resistance to HLA-DM-mediated-dissociation preserves the longevity of those epitopes. We show that immunodominance is established by higher relative abundance of the selected epitopes, which survive Cathepsin digestion either by binding to MHC class II and resisting DM-mediated-dissociation, or being chemically resistant to cathepsins degradation. Non-dominant epitopes are sensitive to both DM and cathepsins and are destroyed.

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