PMID- 35475667
OWN - NLM
STAT- MEDLINE
DCOM- 20220527
LR  - 20220716
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 96
IP  - 10
DP  - 2022 May 25
TI  - Impact of Micropolymorphism Outside the Peptide Binding Groove in the Clinically 
      Relevant Allele HLA-C*14 on T Cell Responses in HIV-1 Infection.
PG  - e0043222
LID - 10.1128/jvi.00432-22 [doi]
LID - e00432-22
AB  - There is increasing evidence for the importance of human leukocyte antigen C 
      (HLA-C)-restricted CD8(+) T cells in HIV-1 control, but these responses are 
      relatively poorly investigated. The number of HLA-C-restricted HIV-1 epitopes 
      identified is much smaller than those of HLA-A-restricted or HLA-B-restricted 
      ones. Here, we utilized a mass spectrometry-based approach to identify HIV-1 
      peptides presented by HLA-C*14:03 protective and HLA-C*14:02 nonprotective 
      alleles. We identified 25 8- to 11-mer HLA-I-bound HIV-1 peptides from 
      HIV-1-infected HLA-C*14:02(+)/14:03(+) cells. Analysis of T cell responses to 
      these peptides identified novel 6 T cell epitopes targeted in HIV-1-infected 
      HLA-C*14:02(+)/14:03(+) subjects. Analyses using HLA stabilization assays 
      demonstrated that all 6 epitope peptides exhibited higher binding to and greater 
      cell surface stabilization of HLA-C*14:02 than HLA-C*14:03. T cell response 
      magnitudes were typically higher in HLA-C*14:02(+) than HLA-C*14:03(+) 
      individuals, with responses to the Pol KM9 and Nef epitopes being significantly 
      higher. The results show that HLA-C*14:02 can elicit stronger T cell responses to 
      HIV-1 than HLA-C*14:03 and suggest that the single amino acid difference between 
      these HLA-C14 subtypes at position 21, outside the peptide-binding groove, 
      indirectly influences the stability of peptide-HLA-C*14 complexes and 
      induction/expansion of HIV-specific T cells. Taken together with a previous 
      finding that KIR2DL2(+) NK cells recognized HLA-C*14:03(+) HIV-1-infected cells 
      more than HLA-C*14:02(+) ones, the present study indicates that these HLA-C*14 
      subtypes differentially impact HIV-1 control by T cells and NK cells. IMPORTANCE 
      Some human leukocyte antigen (HLA) class I alleles are associated with good 
      clinical outcomes in HIV-1 infection and are called protective HLA alleles. 
      Identification of T cell epitopes restricted by protective HLA alleles can give 
      important insight into virus-immune system interactions and inform design of 
      immune-based prophylactic/therapeutic strategies. Although epitopes restricted by 
      many protective HLA-A/B alleles have been identified, protective HLA-C alleles 
      are relatively understudied. Here, we identified 6 novel T cell epitopes 
      presented by both HLA-C*14:02 (no association with protection) and HLA-C*14:03 
      (protective) using a mass spectrometry-based immunopeptidome profiling approach. 
      We found that these peptides bound to and stabilized HLA-C*14:02 better than 
      HLA-C*14:03 and observed differences in induction/expansion of epitope-specific T 
      cell responses in HIV-infected HLA-C*14:02(+) versus HLA-C*14:03(+) individuals. 
      These results enhance understanding of how the microstructural difference at 
      position 21 between these HLA-C*14 subtypes may influence cellular immune 
      responses involved in viral control in HIV-1 infection.
FAU - Chikata, Takayuki
AU  - Chikata T
AD  - Tokyo Laboratory and Division of International Collaboration Research, Joint 
      Research Center for Human Retrovirus Infection, Kumamoto Universitygrid.274841.c, 
      Kumamoto, Japan.
FAU - Paes, Wayne
AU  - Paes W
AD  - Nuffield Department of Clinical Medicine, University of Oxfordgrid.4991.5, 
      Oxford, United Kingdom.
FAU - Kuse, Nozomi
AU  - Kuse N
AD  - Tokyo Laboratory and Division of International Collaboration Research, Joint 
      Research Center for Human Retrovirus Infection, Kumamoto Universitygrid.274841.c, 
      Kumamoto, Japan.
FAU - Partridge, Thomas
AU  - Partridge T
AD  - Nuffield Department of Clinical Medicine, University of Oxfordgrid.4991.5, 
      Oxford, United Kingdom.
FAU - Gatanaga, Hiroyuki
AU  - Gatanaga H
AD  - Tokyo Laboratory and Division of International Collaboration Research, Joint 
      Research Center for Human Retrovirus Infection, Kumamoto Universitygrid.274841.c, 
      Kumamoto, Japan.
AD  - AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, 
      Japan.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Tokyo Laboratory and Division of International Collaboration Research, Joint 
      Research Center for Human Retrovirus Infection, Kumamoto Universitygrid.274841.c, 
      Kumamoto, Japan.
FAU - Kuroki, Kimiko
AU  - Kuroki K
AD  - Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido 
      Universitygrid.39158.36, Sapporo, Japan.
FAU - Maenaka, Katsumi
AU  - Maenaka K
AD  - Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido 
      Universitygrid.39158.36, Sapporo, Japan.
FAU - Ternette, Nicola
AU  - Ternette N
AUID- ORCID: 0000-0002-9283-0743
AD  - Nuffield Department of Clinical Medicine, University of Oxfordgrid.4991.5, 
      Oxford, United Kingdom.
FAU - Oka, Shinichi
AU  - Oka S
AD  - Tokyo Laboratory and Division of International Collaboration Research, Joint 
      Research Center for Human Retrovirus Infection, Kumamoto Universitygrid.274841.c, 
      Kumamoto, Japan.
AD  - AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, 
      Japan.
FAU - Borrow, Persephone
AU  - Borrow P
AD  - Nuffield Department of Clinical Medicine, University of Oxfordgrid.4991.5, 
      Oxford, United Kingdom.
FAU - Takiguchi, Masafumi
AU  - Takiguchi M
AUID- ORCID: 0000-0002-8516-6442
AD  - Tokyo Laboratory and Division of International Collaboration Research, Joint 
      Research Center for Human Retrovirus Infection, Kumamoto Universitygrid.274841.c, 
      Kumamoto, Japan.
LA  - eng
GR  - R01 AI118549/AI/NIAID NIH HHS/United States
GR  - R01 AI 118549/HHS | National Institutes of Health (NIH)/
GR  - MR/K012037/UKRI | Medical Research Council (MRC)/
PT  - Journal Article
DEP - 20220427
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-C Antigens)
RN  - 0 (Peptides)
SB  - IM
MH  - Alleles
MH  - *CD8-Positive T-Lymphocytes/immunology
MH  - Epitopes, T-Lymphocyte
MH  - *HIV Infections/immunology
MH  - *HIV Seropositivity
MH  - HIV-1
MH  - *HLA-C Antigens/genetics
MH  - Humans
MH  - Peptides/metabolism
PMC - PMC9131871
OTO - NOTNLM
OT  - CD8+ T cells
OT  - HIV-1
OT  - HLA-C
OT  - LC-MS/MS
OT  - epitopes
OT  - peptides
COIS- The authors declare no conflict of interest.
EDAT- 2022/04/28 06:00
MHDA- 2022/05/28 06:00
PMCR- 2022/04/27
CRDT- 2022/04/27 12:03
PHST- 2022/04/28 06:00 [pubmed]
PHST- 2022/05/28 06:00 [medline]
PHST- 2022/04/27 12:03 [entrez]
PHST- 2022/04/27 00:00 [pmc-release]
AID - 00432-22 [pii]
AID - jvi.00432-22 [pii]
AID - 10.1128/jvi.00432-22 [doi]
PST - ppublish
SO  - J Virol. 2022 May 25;96(10):e0043222. doi: 10.1128/jvi.00432-22. Epub 2022 Apr 
      27.