PMID- 35235807
OWN - NLM
STAT- MEDLINE
DCOM- 20220411
LR  - 20240214
IS  - 2211-1247 (Electronic)
VI  - 38
IP  - 9
DP  - 2022 Mar 1
TI  - Epitope length variants balance protective immune responses and viral escape in 
      HIV-1 infection.
PG  - 110449
LID - S2211-1247(22)00176-0 [pii]
LID - 10.1016/j.celrep.2022.110449 [doi]
LID - 110449
AB  - Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a single 
      optimal 10-mer epitope (KK10) in the human immunodeficiency virus type-1 (HIV-1) 
      protein p24Gag are associated with enhanced immune control in patients expressing 
      human leukocyte antigen (HLA)-B( *)27:05. We find that proteasomal activity 
      generates multiple length variants of KK10 (4-14 amino acids), which bind TAP and 
      HLA-B( *)27:05. However, only epitope forms >/=8 amino acids evoke peptide 
      length-specific and cross-reactive CTL responses. Structural analyses reveal that 
      all epitope forms bind HLA-B( *)27:05 via a conserved N-terminal motif, and 
      competition experiments show that the truncated epitope forms outcompete 
      immunogenic epitope forms for binding to HLA-B( *)27:05. Common viral escape 
      mutations abolish (L136M) or impair (R132K) production of KK10 and longer epitope 
      forms. Peptide length influences how well the inhibitory NK cell receptor KIR3DL1 
      binds HLA-B( *)27:05 peptide complexes and how intraepitope mutations affect this 
      interaction. These results identify a viral escape mechanism from CTL and NK 
      responses based on differential antigen processing and peptide competition.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Pymm, Phillip
AU  - Pymm P
AD  - Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, 
      Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University 
      of Oxford, Headley Way, Oxford OX3 9DS, UK; Walter and Eliza Hall Institute of 
      Medical Research, University of Melbourne, 1G Royalparade, Parkville, VIC 3052, 
      Australia.
FAU - Tenzer, Stefan
AU  - Tenzer S
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
FAU - Wee, Edmund
AU  - Wee E
AD  - Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, 
      Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University 
      of Oxford, Headley Way, Oxford OX3 9DS, UK.
FAU - Weimershaus, Mirjana
AU  - Weimershaus M
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      Paris Descartes, Sorbonne Paris Cite, Hopital Necker, 149 Rue de Severs, 75015 
      Paris, France; Centre National de la Recherche Scientifique, UMR8253, Universite 
      Paris Descartes, Sorbonne Paris Cite, Hopital Necker, 149 Rue de Severs, 75015 
      Paris, France.
FAU - Burgevin, Anne
AU  - Burgevin A
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      Paris Descartes, Sorbonne Paris Cite, Hopital Necker, 149 Rue de Severs, 75015 
      Paris, France; Centre National de la Recherche Scientifique, UMR8253, Universite 
      Paris Descartes, Sorbonne Paris Cite, Hopital Necker, 149 Rue de Severs, 75015 
      Paris, France.
FAU - Kollnberger, Simon
AU  - Kollnberger S
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      University Hospital of Wales, Heath Park, CF14 4XN Cardiff, UK.
FAU - Gerstoft, Jan
AU  - Gerstoft J
AD  - Department of Infectious Diseases, Rigshospitalet, The National University 
      Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.
FAU - Josephs, Tracy M
AU  - Josephs TM
AD  - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, 381 Royal 
      Parade, Parkville, VIC 3052, Australia.
FAU - Ladell, Kristin
AU  - Ladell K
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      University Hospital of Wales, Heath Park, CF14 4XN Cardiff, UK.
FAU - McLaren, James E
AU  - McLaren JE
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      University Hospital of Wales, Heath Park, CF14 4XN Cardiff, UK.
FAU - Appay, Victor
AU  - Appay V
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1135, Centre 
      d'Immunologie et des Maladies Infectieuses, Sorbonne Universite, Boulevard de 
      l'Hopital, 75013 Paris, France; International Research Center of Medical 
      Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto City 860-0811, 
      Japan.
FAU - Price, David A
AU  - Price DA
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      University Hospital of Wales, Heath Park, CF14 4XN Cardiff, UK; Systems Immunity 
      Research Institute, Cardiff University School of Medicine, University Hospital of 
      Wales, Tenovus Building, CF14 4XN Cardiff, UK.
FAU - Fugger, Lars
AU  - Fugger L
AD  - Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, 
      Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University 
      of Oxford, Headley Way, Oxford OX3 9DS, UK; Medical Research Council Human 
      Immunology Unit, Weatherall Institute of Molecular Medicine, University of 
      Oxford, John Radcliffe Hospital, OX3 9DS Oxford, UK.
FAU - Bell, John I
AU  - Bell JI
AD  - Office of the Regius Professor of Medicine, The Richard Doll Building, University 
      of Oxford, Old Road Campus, OX3 7LF Oxford, UK.
FAU - Schild, Hansjorg
AU  - Schild H
AD  - Institute of Immunology, University Medical Center of the Johannes-Gutenberg 
      University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
FAU - van Endert, Peter
AU  - van Endert P
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 1151, Universite 
      Paris Descartes, Sorbonne Paris Cite, Hopital Necker, 149 Rue de Severs, 75015 
      Paris, France; Centre National de la Recherche Scientifique, UMR8253, Universite 
      Paris Descartes, Sorbonne Paris Cite, Hopital Necker, 149 Rue de Severs, 75015 
      Paris, France.
FAU - Harkiolaki, Maria
AU  - Harkiolaki M
AD  - Structural Biology Group, Wellcome Trust Centre for Human Genetics, University of 
      Oxford, Old Road Campus, OX3 7LF Oxford, UK; Diamond Light Source, Harwell 
      Science and Innovation Campus, Fermi Avenue, OX11 0DE Didcot, UK.
FAU - Iversen, Astrid K N
AU  - Iversen AKN
AD  - Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, 
      Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University 
      of Oxford, Headley Way, Oxford OX3 9DS, UK. Electronic address: 
      astrid.iversen@ndcn.ox.ac.uk.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Amino Acids)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Peptides)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acids
MH  - Antigen Presentation
MH  - Epitopes, T-Lymphocyte
MH  - *HIV Infections
MH  - *HIV-1
MH  - HLA-B Antigens/genetics
MH  - Humans
MH  - Peptides
PMC - PMC9631117
OTO - NOTNLM
OT  - HIV-1
OT  - HLA-B( *)27:05
OT  - KIR3DL1
OT  - crystal structures
OT  - cytotoxic T lymphocytes
OT  - differential antigen processing
OT  - immune-response inhibition
OT  - natural killer cells
OT  - peptide competition
OT  - viral escape
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2022/03/03 06:00
MHDA- 2022/04/12 06:00
PMCR- 2022/03/01
CRDT- 2022/03/02 20:06
PHST- 2020/04/23 00:00 [received]
PHST- 2021/10/31 00:00 [revised]
PHST- 2022/02/07 00:00 [accepted]
PHST- 2022/03/02 20:06 [entrez]
PHST- 2022/03/03 06:00 [pubmed]
PHST- 2022/04/12 06:00 [medline]
PHST- 2022/03/01 00:00 [pmc-release]
AID - S2211-1247(22)00176-0 [pii]
AID - 110449 [pii]
AID - 10.1016/j.celrep.2022.110449 [doi]
PST - ppublish
SO  - Cell Rep. 2022 Mar 1;38(9):110449. doi: 10.1016/j.celrep.2022.110449.