PMID- 29437277 OWN - NLM STAT- MEDLINE DCOM- 20190816 LR - 20190816 IS - 1615-9861 (Electronic) IS - 1615-9853 (Linking) VI - 18 IP - 12 DP - 2018 Jun TI - Identification of Native and Posttranslationally Modified HLA-B*57:01-Restricted HIV Envelope Derived Epitopes Using Immunoproteomics. PG - e1700253 LID - 10.1002/pmic.201700253 [doi] AB - The recognition of pathogen-derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the ER. These peptide-HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T-cells leading to the eradication of the infected cell. Here, naturally presented HLA-B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv) are identified. HIVenv peptides are present at a very small percentage of the overall HLA-B*57:01 peptidome (<0.1%) and both native and posttranslationally modified forms of two distinct HIV peptides are identified. Notably, a peptide bearing a natively encoded C-terminal tryptophan residue is also present in a modified form containing a kynurenine residue. Kynurenine is a major product of tryptophan catabolism and is abundant during inflammation and infection. Binding of these peptides at a molecular level and their immunogenicity in preliminary functional studies are examined. Modest immune responses are observed to the modified HIVenv peptide, highlighting a potential role for kynurenine-modified peptides in the immune response to HIV and other viral infections. CI - (c) 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Ramarathinam, Sri H AU - Ramarathinam SH AUID- ORCID: 0000-0002-2787-1282 AD - Infection and Immunity Program, Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia. FAU - Gras, Stephanie AU - Gras S AD - Infection and Immunity Program, Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia. AD - ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia. FAU - Alcantara, Sheilajen AU - Alcantara S AD - Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Australia. FAU - Yeung, Amanda W S AU - Yeung AWS AD - Mechanisms of Disease and Translational Medicine, Department of Pathology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia. FAU - Mifsud, Nicole A AU - Mifsud NA AD - Infection and Immunity Program, Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia. FAU - Sonza, Secondo AU - Sonza S AD - Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Australia. FAU - Illing, Patricia T AU - Illing PT AD - Infection and Immunity Program, Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia. FAU - Glaros, Elias N AU - Glaros EN AD - Mechanisms of Disease and Translational Medicine, Department of Pathology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia. FAU - Center, Robert J AU - Center RJ AD - Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Australia. AD - Burnet Institute, Melbourne, Australia. FAU - Thomas, Shane R AU - Thomas SR AD - Mechanisms of Disease and Translational Medicine, Department of Pathology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia. FAU - Kent, Stephen J AU - Kent SJ AD - Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Australia. AD - Melbourne Sexual Health Centre, Central Clinical School, Monash University, Melbourne, Australia. AD - ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia. FAU - Ternette, Nicola AU - Ternette N AUID- ORCID: 0000-0002-9283-0743 AD - The Jenner Institute, Target Discovery Institute Mass Spectrometry Laboratory, University of Oxford, Oxford, UK. FAU - Purcell, Damian F J AU - Purcell DFJ AD - Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Australia. FAU - Rossjohn, Jamie AU - Rossjohn J AD - Infection and Immunity Program, Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia. AD - ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia. AD - Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. FAU - Purcell, Anthony W AU - Purcell AW AUID- ORCID: 0000-0003-0532-8331 AD - Infection and Immunity Program, Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180410 PL - Germany TA - Proteomics JT - Proteomics JID - 101092707 RN - 0 (Epitopes) RN - 0 (Gene Products, env) RN - 0 (HIV Antigens) RN - 0 (HLA-B Antigens) RN - 0 (HLA-B57 antigen) CIN - Proteomics. 2018 Jun;18(12):e1800041. PMID: 29513933 MH - B-Lymphocytes/*immunology/virology MH - Cells, Cultured MH - Epitopes/*immunology/metabolism MH - Gene Products, env/*immunology/metabolism MH - HIV Antigens/*immunology/metabolism MH - HIV Infections/immunology/virology MH - HIV-1/*immunology MH - HLA-B Antigens/chemistry/*immunology/metabolism MH - Humans MH - *Protein Processing, Post-Translational OTO - NOTNLM OT - HLA-B*57:01 OT - human immunodeficiency virus OT - immunopeptidome OT - kynurenine OT - posttranslational modification EDAT- 2018/02/14 06:00 MHDA- 2019/08/17 06:00 CRDT- 2018/02/14 06:00 PHST- 2017/10/27 00:00 [received] PHST- 2018/01/29 00:00 [revised] PHST- 2018/02/14 06:00 [pubmed] PHST- 2019/08/17 06:00 [medline] PHST- 2018/02/14 06:00 [entrez] AID - 10.1002/pmic.201700253 [doi] PST - ppublish SO - Proteomics. 2018 Jun;18(12):e1700253. doi: 10.1002/pmic.201700253. Epub 2018 Apr 10.