PMID- 25810538
OWN - NLM
STAT- MEDLINE
DCOM- 20150727
LR  - 20220129
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 89
IP  - 11
DP  - 2015 Jun
TI  - Early Kinetics of the HLA Class I-Associated Peptidome of MVA.HIVconsv-Infected 
      Cells.
PG  - 5760-71
LID - 10.1128/JVI.03627-14 [doi]
AB  - Cytotoxic T cells substantially contribute to the control of intracellular 
      pathogens such as human immunodeficiency virus type 1 (HIV-1). Here, we evaluated 
      the immunopeptidome of Jurkat cells infected with the vaccine candidate 
      MVA.HIVconsv, which delivers HIV-1 conserved antigenic regions by using modified 
      vaccinia virus Ankara (MVA). We employed liquid chromatography-tandem mass 
      spectrometry (LC-MS/MS) to identify 6,358 unique peptides associated with the 
      class I human leukocyte antigen (HLA), of which 98 peptides were derived from the 
      MVA vector and 7 were derived from the HIVconsv immunogen. Human vaccine 
      recipients responded to the peptide sequences identified by LC-MS/MS. Peptides 
      derived from the conserved HIV-1 regions were readily detected as early as 1.5 h 
      after MVA.HIVconsv infection. Four of the seven conserved peptides were monitored 
      between 0 and 3.5 h of infection by using quantitative mass spectrometry (Q-MS), 
      and their abundance in HLA class I associations reflected levels of the whole 
      HIVconsv protein in the cell. While immunopeptides delivered by the incoming MVA 
      vector proteins could be detected, all early HIVconsv-derived immunopeptides were 
      likely synthesized de novo. MVA.HIVconsv infection generally altered the 
      composition of HLA class I-associated human (self) peptides, but these changes 
      corresponded only partially to changes in the whole cell host protein abundance. 
      IMPORTANCE: The vast changes in cellular antigen presentation after infection of 
      cells with a vectored vaccine, as shown here for MVA.HIVconsv, highlight the 
      complexity of factors that need to be considered for efficient antigen delivery 
      and presentation. Identification and quantitation of HLA class I-associated 
      peptides by Q-MS will not only find broad application in T-cell epitope discovery 
      but also inform vaccine design and allow evaluation of efficient epitope 
      presentation using different delivery strategies.
CI  - Copyright (c) 2015, Ternette et al.
FAU - Ternette, Nicola
AU  - Ternette N
AUID- ORCID: 0000-0002-9283-0743
AD  - The Jenner Institute, Nuffield Department of Medicine, University of Oxford, 
      Oxford, United Kingdom Target Discovery Institute, Nuffield Department of 
      Medicine, University of Oxford, Oxford, United Kingdom 
      nicola.ternette@ndm.ox.ac.uk.
FAU - Block, Peter D
AU  - Block PD
AD  - The Jenner Institute, Nuffield Department of Medicine, University of Oxford, 
      Oxford, United Kingdom Target Discovery Institute, Nuffield Department of 
      Medicine, University of Oxford, Oxford, United Kingdom.
FAU - Sanchez-Bernabeu, Alvaro
AU  - Sanchez-Bernabeu A
AD  - Target Discovery Institute, Nuffield Department of Medicine, University of 
      Oxford, Oxford, United Kingdom Universitat de Barcelona, Barcelona, Spain.
FAU - Borthwick, Nicola
AU  - Borthwick N
AD  - The Jenner Institute, Nuffield Department of Medicine, University of Oxford, 
      Oxford, United Kingdom.
FAU - Pappalardo, Elisa
AU  - Pappalardo E
AD  - Sir William Dunn School of Pathology, University of Oxford, Oxford, United 
      Kingdom.
FAU - Abdul-Jawad, Sultan
AU  - Abdul-Jawad S
AD  - The Jenner Institute, Nuffield Department of Medicine, University of Oxford, 
      Oxford, United Kingdom.
FAU - Ondondo, Beatrice
AU  - Ondondo B
AD  - The Jenner Institute, Nuffield Department of Medicine, University of Oxford, 
      Oxford, United Kingdom.
FAU - Charles, Philip D
AU  - Charles PD
AD  - Target Discovery Institute, Nuffield Department of Medicine, University of 
      Oxford, Oxford, United Kingdom.
FAU - Dorrell, Lucy
AU  - Dorrell L
AD  - The Jenner Institute, Nuffield Department of Medicine, University of Oxford, 
      Oxford, United Kingdom.
FAU - Kessler, Benedikt M
AU  - Kessler BM
AD  - Target Discovery Institute, Nuffield Department of Medicine, University of 
      Oxford, Oxford, United Kingdom.
FAU - Hanke, Tomas
AU  - Hanke T
AD  - The Jenner Institute, Nuffield Department of Medicine, University of Oxford, 
      Oxford, United Kingdom.
LA  - eng
GR  - G1001757/MRC_/Medical Research Council/United Kingdom
GR  - MC_U137884179/MRC_/Medical Research Council/United Kingdom
GR  - MRC G1001757/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150325
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (AIDS Vaccines)
RN  - 0 (Antigens, Viral)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
RN  - 0 (Vaccines, Synthetic)
SB  - IM
MH  - AIDS Vaccines/*immunology
MH  - Antigens, Viral/*analysis
MH  - Chromatography, Liquid
MH  - Genetic Vectors
MH  - HIV-1/*immunology
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Jurkat Cells
MH  - Peptides/*analysis
MH  - T-Lymphocytes, Cytotoxic/*chemistry/immunology
MH  - Tandem Mass Spectrometry
MH  - Time Factors
MH  - Vaccines, Synthetic/immunology
MH  - Vaccinia virus/genetics/immunology
PMC - PMC4442425
EDAT- 2015/03/27 06:00
MHDA- 2015/07/28 06:00
PMCR- 2015/03/25
CRDT- 2015/03/27 06:00
PHST- 2014/12/19 00:00 [received]
PHST- 2015/03/09 00:00 [accepted]
PHST- 2015/03/27 06:00 [entrez]
PHST- 2015/03/27 06:00 [pubmed]
PHST- 2015/07/28 06:00 [medline]
PHST- 2015/03/25 00:00 [pmc-release]
AID - JVI.03627-14 [pii]
AID - 03627-14 [pii]
AID - 10.1128/JVI.03627-14 [doi]
PST - ppublish
SO  - J Virol. 2015 Jun;89(11):5760-71. doi: 10.1128/JVI.03627-14. Epub 2015 Mar 25.