title: Viral infection causes a shift in the self peptide repertoire presented by human MHC class I molecules.
abstract: OBJECTIVE
  MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism.
  
  
  METHODS
  The self peptide repertoire presented by HLA-A*01;01, HLA-A*02;01, HLA-B*07;02, HLA-B*35;01, and HLA-B*45;01 (where HLA is human leukocyte antigen) was determined by tandem MS before and after vaccinia virus infection.
  
  
  RESULTS
  We observed a profound alteration in the self peptide repertoire with hundreds of self peptides uniquely presented after infection for which we have coined the term "self peptidome shift." The fraction of novel self peptides presented following infection varied for different HLA class I molecules. A large part (approximately 40%) of the self peptidome shift arose from peptides derived from type I interferon-inducible genes, consistent with cellular responses to viral infection. Interestingly, approximately 12% of self peptides presented after infection showed allelic variation when searched against approximately 300 human genomes.
  
  
  CONCLUSIONS
  Self peptidome shift in a clinical transplant setting could result in alloreactivity by presenting new self peptides in the context of infection-induced inflammation.
authors.affiliation: Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Spencer
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Jelena S
authors.initials: JS
authors.lastname: Bezbradica
authors.affiliation: Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA.
authors.forename: Mireya G
authors.initials: MG
authors.lastname: Ramos
authors.affiliation: Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA.
authors.forename: Chenoa D
authors.initials: CD
authors.lastname: Arico
authors.affiliation: Department of Pathology, Microbiology and Immunology, Nashville, TN, USA.
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Conant
authors.affiliation: Department of Pathology, Microbiology and Immunology, Nashville, TN, USA.|Veterans Administration Tennessee Valley Healthcare System, Nashville, TN, USA.
authors.forename: Pavlo
authors.initials: P
authors.lastname: Gilchuk
authors.affiliation: Department of Pathology, Microbiology and Immunology, Nashville, TN, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Gray
authors.affiliation: Department of Pathology, Microbiology and Immunology, Nashville, TN, USA.|Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Mu
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Microbiology and Immunology, Nashville, TN, USA.|Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Xinnan
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Science Centre, Oklahoma City, OK, USA.
authors.forename: William
authors.initials: W
authors.lastname: Hildebrand
authors.affiliation: Department of Pathology, Microbiology and Immunology, Nashville, TN, USA.|Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Link
authors.affiliation: Department of Pathology, Microbiology and Immunology, Nashville, TN, USA.|Veterans Administration Tennessee Valley Healthcare System, Nashville, TN, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009857:Oncogenes; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D040901:Proteomics; D014616:Vaccinia virus / Q000276:immunology / Q000502:physiology*
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides
keywords: Infection; Minor histocompatibility; Peptidome; Self peptides; Transplantation