PMID- 29780384
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20220129
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Discrimination Between Human Leukocyte Antigen Class I-Bound and Co-Purified 
      HIV-Derived Peptides in Immunopeptidomics Workflows.
PG  - 912
LID - 10.3389/fimmu.2018.00912 [doi]
LID - 912
AB  - Elucidation of novel peptides presented by human leukocyte antigen (HLA) class I 
      alleles by immunopeptidomics constitutes a powerful approach that can inform the 
      rational design of CD8(+) T cell inducing vaccines to control infection with 
      pathogens such as human immunodeficiency virus type 1 (HIV-1) or to combat 
      tumors. Recent advances in the sensitivity of liquid chromatography tandem mass 
      spectrometry instrumentation have facilitated the discovery of thousands of 
      natural HLA-restricted peptides in a single measurement. However, the extent of 
      contamination of class I-bound peptides identified using HLA immunoprecipitation 
      (IP)-based immunopeptidomics approaches with peptides from other sources has not 
      previously been evaluated in depth. Here, we investigated the specificity of the 
      IP-based immunopeptidomics methodology using HLA class I- or II-deficient cell 
      lines and membrane protein-specific antibody IPs. We demonstrate that the 721.221 
      B lymphoblastoid cell line, widely regarded to be HLA class Ia-deficient, 
      actually expresses and presents peptides on HLA-C*01:02. Using this cell line and 
      the C8166 (HLA class I- and II-expressing) cell line, we show that some HLA class 
      II-bound peptides were co-purified non-specifically during HLA class I and 
      membrane protein IPs. Furthermore, IPs of "irrelevant" membrane proteins from 
      HIV-1-infected HLA class I- and/or II-expressing cells revealed that unusually 
      long HIV-1-derived peptides previously reported by us and other immunopeptidomics 
      studies as potentially novel CD8(+) T cell epitopes were non-specifically 
      co-isolated, and so constitute a source of contamination in HLA class I IPs. For 
      example, a 16-mer (FLGKIWPSYKGRPGNF), which was detected in all samples studied 
      represents the full p1 segment of the abundant intracellular or virion-associated 
      proteolytically-processed HIV-1 Gag protein. This result is of importance, as 
      these long co-purified HIV-1 Gag peptides may not elicit CD8(+) T cell responses 
      when incorporated into candidate vaccines. These results have wider implications 
      for HLA epitope discovery from abundant or membrane-associated antigens by 
      immunopeptidomics in the context of infectious diseases, cancer, and 
      autoimmunity.
FAU - Partridge, Thomas
AU  - Partridge T
AD  - Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
FAU - Nicastri, Annalisa
AU  - Nicastri A
AD  - Nuffield Department of Medicine, Target Discovery Institute, University of 
      Oxford, Oxford, United Kingdom.
FAU - Kliszczak, Anna E
AU  - Kliszczak AE
AD  - Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
FAU - Yindom, Louis-Marie
AU  - Yindom LM
AD  - Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
FAU - Kessler, Benedikt M
AU  - Kessler BM
AD  - Nuffield Department of Medicine, Target Discovery Institute, University of 
      Oxford, Oxford, United Kingdom.
FAU - Ternette, Nicola
AU  - Ternette N
AD  - Nuffield Department of Medicine, Target Discovery Institute, University of 
      Oxford, Oxford, United Kingdom.
AD  - The Jenner Institute, Target Discovery Institute Mass Spectrometry Laboratory, 
      University of Oxford, Oxford, United Kingdom.
FAU - Borrow, Persephone
AU  - Borrow P
AD  - Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
LA  - eng
GR  - MR/K012037/1/MRC_/Medical Research Council/United Kingdom
GR  - R01 AI118549/AI/NIAID NIH HHS/United States
GR  - MR/K012037/Medical Research Council/United Kingdom
GR  - MR/N023668/1/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180427
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (gag Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - HIV-1/*immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Immunoprecipitation
MH  - Mass Spectrometry
MH  - *Proteomics
MH  - Workflow
MH  - gag Gene Products, Human Immunodeficiency Virus/*immunology
PMC - PMC5946011
OTO - NOTNLM
OT  - HIV
OT  - antigen presentation
OT  - epitope
OT  - human leukocyte antigen
OT  - immunopeptidomics
OT  - major histocompatibility complex
OT  - mass spectrometry
EDAT- 2018/05/22 06:00
MHDA- 2018/05/22 06:01
PMCR- 2018/01/01
CRDT- 2018/05/22 06:00
PHST- 2018/01/12 00:00 [received]
PHST- 2018/04/12 00:00 [accepted]
PHST- 2018/05/22 06:00 [entrez]
PHST- 2018/05/22 06:00 [pubmed]
PHST- 2018/05/22 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.00912 [doi]
PST - epublish
SO  - Front Immunol. 2018 Apr 27;9:912. doi: 10.3389/fimmu.2018.00912. eCollection 
      2018.