PMID- 30479346
OWN - NLM
STAT- MEDLINE
DCOM- 20181231
LR  - 20191127
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Nov 27
TI  - Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag 
      escape variants.
PG  - 5023
LID - 10.1038/s41467-018-07209-7 [doi]
LID - 5023
AB  - Some closely related human leukocyte antigen (HLA) alleles are associated with 
      variable clinical outcomes following HIV-1 infection despite presenting the same 
      viral epitopes. Mechanisms underlying these differences remain unclear but may be 
      due to intrinsic characteristics of the HLA alleles or responding T cell 
      repertoires. Here we examine CD8(+) T cell responses against the immunodominant 
      HIV-1 Gag epitope TL9 (TPQDLNTML(180-188)) in the context of the protective 
      allele B*81:01 and the less protective allele B*42:01. We observe a population of 
      dual-reactive T cells that recognize TL9 presented by both B*81:01 and B*42:01 in 
      individuals lacking one allele. The presence of dual-reactive T cells is 
      associated with lower plasma viremia, suggesting a clinical benefit. In B*42:01 
      expressing individuals, the dual-reactive phenotype defines public T cell 
      receptor (TCR) clones that recognize a wider range of TL9 escape variants, 
      consistent with enhanced control of viral infection through containment of HIV-1 
      sequence adaptation.
FAU - Ogunshola, Funsho
AU  - Ogunshola F
AD  - Africa Health Research Institute, University of KwaZulu-Natal, Durban, South 
      Africa.
AD  - HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of 
      KwaZulu-Natal, Durban, South Africa.
FAU - Anmole, Gursev
AU  - Anmole G
AD  - Department of Molecular Biology and Biochemistry, Simon Fraser University, 
      Burnaby, BC, V5A 1S6, Canada.
FAU - Miller, Rachel L
AU  - Miller RL
AD  - Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, V5A 1S6, 
      Canada.
FAU - Goering, Emily
AU  - Goering E
AD  - Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.
FAU - Nkosi, Thandeka
AU  - Nkosi T
AD  - Africa Health Research Institute, University of KwaZulu-Natal, Durban, South 
      Africa.
AD  - HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of 
      KwaZulu-Natal, Durban, South Africa.
FAU - Muema, Daniel
AU  - Muema D
AD  - Africa Health Research Institute, University of KwaZulu-Natal, Durban, South 
      Africa.
FAU - Mann, Jaclyn
AU  - Mann J
AD  - HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of 
      KwaZulu-Natal, Durban, South Africa.
FAU - Ismail, Nasreen
AU  - Ismail N
AD  - HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of 
      KwaZulu-Natal, Durban, South Africa.
FAU - Chopera, Denis
AU  - Chopera D
AD  - Africa Health Research Institute, University of KwaZulu-Natal, Durban, South 
      Africa.
FAU - Ndung'u, Thumbi
AU  - Ndung'u T
AD  - Africa Health Research Institute, University of KwaZulu-Natal, Durban, South 
      Africa.
AD  - HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of 
      KwaZulu-Natal, Durban, South Africa.
AD  - Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.
AD  - Max Planck Institute for Infection Biology, Berlin, Germany.
FAU - Brockman, Mark A
AU  - Brockman MA
AUID- ORCID: 0000-0001-6432-1426
AD  - Department of Molecular Biology and Biochemistry, Simon Fraser University, 
      Burnaby, BC, V5A 1S6, Canada. mark_brockman@sfu.ca.
AD  - Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, V5A 1S6, 
      Canada. mark_brockman@sfu.ca.
AD  - British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, V6Z 1Y6, 
      Canada. mark_brockman@sfu.ca.
FAU - Ndhlovu, Zaza M
AU  - Ndhlovu ZM
AUID- ORCID: 0000-0002-2708-3315
AD  - Africa Health Research Institute, University of KwaZulu-Natal, Durban, South 
      Africa. zndhlovu@mgh.harvard.edu.
AD  - HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of 
      KwaZulu-Natal, Durban, South Africa. zndhlovu@mgh.harvard.edu.
AD  - Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA. 
      zndhlovu@mgh.harvard.edu.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - R01 AI102660/AI/NIAID NIH HHS/United States
GR  - R37 AI080289/AI/NIAID NIH HHS/United States
GR  - UM1 AI126617/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181127
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (HLA-B Antigens)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (gag Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Clone Cells
MH  - Female
MH  - HIV-1/*metabolism
MH  - HLA-B Antigens/*immunology
MH  - Humans
MH  - Male
MH  - Mutation/*genetics
MH  - Receptors, Antigen, T-Cell/*metabolism
MH  - Reproducibility of Results
MH  - Viral Load
MH  - Young Adult
MH  - gag Gene Products, Human Immunodeficiency Virus/chemistry/*genetics
PMC - PMC6258674
COIS- The authors declare no competing interests.
EDAT- 2018/11/28 06:00
MHDA- 2019/01/01 06:00
PMCR- 2018/11/27
CRDT- 2018/11/28 06:00
PHST- 2018/04/18 00:00 [received]
PHST- 2018/10/16 00:00 [accepted]
PHST- 2018/11/28 06:00 [entrez]
PHST- 2018/11/28 06:00 [pubmed]
PHST- 2019/01/01 06:00 [medline]
PHST- 2018/11/27 00:00 [pmc-release]
AID - 10.1038/s41467-018-07209-7 [pii]
AID - 7209 [pii]
AID - 10.1038/s41467-018-07209-7 [doi]
PST - epublish
SO  - Nat Commun. 2018 Nov 27;9(1):5023. doi: 10.1038/s41467-018-07209-7.