PMID- 37217466
OWN - NLM
STAT- MEDLINE
DCOM- 20230524
LR  - 20230612
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 May 22
TI  - Molecular basis of differential HLA class I-restricted T cell recognition of a 
      highly networked HIV peptide.
PG  - 2929
LID - 10.1038/s41467-023-38573-8 [doi]
LID - 2929
AB  - Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting 
      highly networked epitopes in complex with human-leukocyte-antigen-class-I 
      (HLA-I). However, the extent to which the presenting HLA allele contributes to 
      this process is unknown. Here we examine the CTL response to QW9, a highly 
      networked epitope presented by the disease-protective HLA-B57 and disease-neutral 
      HLA-B53. Despite robust targeting of QW9 in persons expressing either allele, T 
      cell receptor (TCR) cross-recognition of the naturally occurring variant QW9_S3T 
      is consistently reduced when presented by HLA-B53 but not by HLA-B57. Crystal 
      structures show substantial conformational changes from QW9-HLA to QW9_S3T-HLA by 
      both alleles. The TCR-QW9-B53 ternary complex structure manifests how the QW9-B53 
      can elicit effective CTLs and suggests sterically hindered cross-recognition by 
      QW9_S3T-B53. We observe populations of cross-reactive TCRs for B57, but not B53 
      and also find greater peptide-HLA stability for B57 in comparison to B53. These 
      data demonstrate differential impacts of HLAs on TCR cross-recognition and 
      antigen presentation of a naturally arising variant, with important implications 
      for vaccine design.
CI  - (c) 2023. The Author(s).
FAU - Li, Xiaolong
AU  - Li X
AUID- ORCID: 0000-0001-6549-4089
AD  - School of Life Sciences, Division of Life Sciences and Medicine, University of 
      Science and Technology of China, Hefei, Anhui, 230027, China. 
      xiaolong@crystal.harvard.edu.
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA. 
      xiaolong@crystal.harvard.edu.
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02215, USA. xiaolong@crystal.harvard.edu.
FAU - Singh, Nishant Kumar
AU  - Singh NK
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
AD  - Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02142, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA.
FAU - Collins, David R
AU  - Collins DR
AUID- ORCID: 0000-0001-7903-346X
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA.
FAU - Ng, Robert
AU  - Ng R
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02215, USA.
FAU - Zhang, Angela
AU  - Zhang A
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02215, USA.
FAU - Lamothe-Molina, Pedro A
AU  - Lamothe-Molina PA
AUID- ORCID: 0000-0001-9262-2920
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
FAU - Shahinian, Peter
AU  - Shahinian P
AUID- ORCID: 0000-0003-0435-2583
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
FAU - Xu, Shutong
AU  - Xu S
AUID- ORCID: 0000-0002-9894-1735
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02215, USA.
FAU - Tan, Kemin
AU  - Tan K
AUID- ORCID: 0000-0002-4003-7903
AD  - Structural Biology Center, X-ray Science Division, Advanced Photon Source, 
      Argonne National Laboratory, Lemont, IL, 60439, USA.
FAU - Piechocka-Trocha, Alicja
AU  - Piechocka-Trocha A
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA.
FAU - Urbach, Jonathan M
AU  - Urbach JM
AUID- ORCID: 0000-0003-0597-2848
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
FAU - Weber, Jeffrey K
AU  - Weber JK
AD  - IBM Thomas J. Watson Research Center, Computational Biology Center, Yorktown 
      Heights, NY, 10598, USA.
FAU - Gaiha, Gaurav D
AU  - Gaiha GD
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
AD  - Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, 02114, 
      USA.
FAU - Takou Mbah, Overbeck Christian
AU  - Takou Mbah OC
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
FAU - Huynh, Tien
AU  - Huynh T
AD  - IBM Thomas J. Watson Research Center, Computational Biology Center, Yorktown 
      Heights, NY, 10598, USA.
FAU - Cheever, Sophia
AU  - Cheever S
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
FAU - Chen, James
AU  - Chen J
AUID- ORCID: 0000-0001-6039-613X
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
FAU - Birnbaum, Michael
AU  - Birnbaum M
AUID- ORCID: 0000-0002-2281-3518
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
AD  - Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, 02142, USA.
FAU - Zhou, Ruhong
AU  - Zhou R
AUID- ORCID: 0000-0001-8624-5591
AD  - IBM Thomas J. Watson Research Center, Computational Biology Center, Yorktown 
      Heights, NY, 10598, USA.
AD  - Department of Chemistry, Columbia University, New York, NY, 10025, USA.
AD  - Institute of Quantitative Biology, College of Life Sciences, Zhejiang University, 
      Hangzhou, Zhejiang, 310058, China.
FAU - Walker, Bruce D
AU  - Walker BD
AUID- ORCID: 0000-0001-6122-9245
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA. 
      bwalker@mgh.harvard.edu.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA. 
      bwalker@mgh.harvard.edu.
AD  - Institute for Medical Engineering and Science and Department of Biology, 
      Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. 
      bwalker@mgh.harvard.edu.
FAU - Wang, Jia-Huai
AU  - Wang JH
AUID- ORCID: 0000-0003-3478-829X
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02215, USA. jwang@crystal.harvard.edu.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA, 02215, USA. 
      jwang@crystal.harvard.edu.
AD  - Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical 
      School, Boston, MA, 02215, USA. jwang@crystal.harvard.edu.
LA  - eng
GR  - P01 HL103526/HL/NHLBI NIH HHS/United States
GR  - P30 AI060354/AI/NIAID NIH HHS/United States
GR  - R01 AI149704/AI/NIAID NIH HHS/United States
GR  - UM1 AI144462/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230522
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (HLA-B Antigens)
RN  - 0 (Peptides)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Humans
MH  - *HIV Infections
MH  - HLA-B Antigens/genetics
MH  - T-Lymphocytes, Cytotoxic
MH  - Peptides
MH  - Epitopes, T-Lymphocyte
MH  - Receptors, Antigen, T-Cell
PMC - PMC10202051
COIS- The authors declare no competing interests.
EDAT- 2023/05/23 01:06
MHDA- 2023/05/24 06:42
PMCR- 2023/05/22
CRDT- 2023/05/22 23:13
PHST- 2022/05/02 00:00 [received]
PHST- 2023/05/09 00:00 [accepted]
PHST- 2023/05/24 06:42 [medline]
PHST- 2023/05/23 01:06 [pubmed]
PHST- 2023/05/22 23:13 [entrez]
PHST- 2023/05/22 00:00 [pmc-release]
AID - 10.1038/s41467-023-38573-8 [pii]
AID - 38573 [pii]
AID - 10.1038/s41467-023-38573-8 [doi]
PST - epublish
SO  - Nat Commun. 2023 May 22;14(1):2929. doi: 10.1038/s41467-023-38573-8.