PMID- 37468623
OWN - NLM
STAT- MEDLINE
DCOM- 20230808
LR  - 20240228
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 620
IP  - 7972
DP  - 2023 Aug
TI  - A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection.
PG  - 128-136
LID - 10.1038/s41586-023-06331-x [doi]
AB  - Studies have demonstrated that at least 20% of individuals infected with 
      SARS-CoV-2 remain asymptomatic(1-4). Although most global efforts have focused on 
      severe illness in COVID-19, examining asymptomatic infection provides a unique 
      opportunity to consider early immunological features that promote rapid viral 
      clearance. Here, postulating that variation in the human leukocyte antigen (HLA) 
      loci may underly processes mediating asymptomatic infection, we enrolled 29,947 
      individuals, for whom high-resolution HLA genotyping data were available, in a 
      smartphone-based study designed to track COVID-19 symptoms and outcomes. Our 
      discovery cohort (n = 1,428) comprised unvaccinated individuals who reported a 
      positive test result for SARS-CoV-2. We tested for association of five HLA loci 
      with disease course and identified a strong association between HLA-B*15:01 and 
      asymptomatic infection, observed in two independent cohorts. Suggesting that this 
      genetic association is due to pre-existing T cell immunity, we show that T cells 
      from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to 
      the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the 
      reactive T cells displayed a memory phenotype, were highly polyfunctional and 
      were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal 
      structure of HLA-B*15:01-peptide complexes demonstrates that the peptides 
      NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to 
      be stabilized and presented by HLA-B*15:01. Finally, we show that the structural 
      similarity of the peptides underpins T cell cross-reactivity of high-affinity 
      public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated 
      pre-existing immunity.
CI  - (c) 2023. The Author(s).
FAU - Augusto, Danillo G
AU  - Augusto DG
AUID- ORCID: 0000-0001-5665-8547
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California, San Francisco, CA, USA.
AD  - Department of Biological Sciences, The University of North Carolina at Charlotte, 
      Charlotte, NC, USA.
AD  - Programa de Pos-Graduacao em Genetica, Universidade Federal do Parana, Curitiba, 
      Brazil.
FAU - Murdolo, Lawton D
AU  - Murdolo LD
AUID- ORCID: 0000-0001-5222-9585
AD  - Department of Biochemistry and Chemistry, La Trobe Institute for Molecular 
      Science, La Trobe University, Bundoora, Victoria, Australia.
FAU - Chatzileontiadou, Demetra S M
AU  - Chatzileontiadou DSM
AUID- ORCID: 0000-0003-1132-8952
AD  - Department of Biochemistry and Chemistry, La Trobe Institute for Molecular 
      Science, La Trobe University, Bundoora, Victoria, Australia.
AD  - Department of Biochemistry and Molecular Biology, Biomedicine Discovery 
      Institute, Monash University, Clayton, Victoria, Australia.
FAU - Sabatino, Joseph J Jr
AU  - Sabatino JJ Jr
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California, San Francisco, CA, USA.
FAU - Yusufali, Tasneem
AU  - Yusufali T
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California, San Francisco, CA, USA.
FAU - Peyser, Noah D
AU  - Peyser ND
AUID- ORCID: 0000-0003-4529-8325
AD  - Division of Cardiology, Department of Medicine, University of California, San 
      Francisco, CA, USA.
FAU - Butcher, Xochitl
AU  - Butcher X
AD  - Division of Cardiology, Department of Medicine, University of California, San 
      Francisco, CA, USA.
FAU - Kizer, Kerry
AU  - Kizer K
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California, San Francisco, CA, USA.
FAU - Guthrie, Karoline
AU  - Guthrie K
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California, San Francisco, CA, USA.
FAU - Murray, Victoria W
AU  - Murray VW
AUID- ORCID: 0000-0002-4479-2359
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Pae, Vivian
AU  - Pae V
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Sarvadhavabhatla, Sannidhi
AU  - Sarvadhavabhatla S
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Beltran, Fiona
AU  - Beltran F
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Gill, Gurjot S
AU  - Gill GS
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Lynch, Kara L
AU  - Lynch KL
AD  - Department of Laboratory Medicine, University of California, San Francisco, CA, 
      USA.
FAU - Yun, Cassandra
AU  - Yun C
AUID- ORCID: 0000-0002-6971-2060
AD  - Department of Laboratory Medicine, University of California, San Francisco, CA, 
      USA.
FAU - Maguire, Colin T
AU  - Maguire CT
AUID- ORCID: 0000-0001-7890-8375
AD  - Clinical and Translational Science Institute, University of Utah, Salt Lake City, 
      UT, USA.
FAU - Peluso, Michael J
AU  - Peluso MJ
AUID- ORCID: 0000-0003-0585-6230
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Hoh, Rebecca
AU  - Hoh R
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Henrich, Timothy J
AU  - Henrich TJ
AD  - Division of Experimental Medicine, Department of Medicine, University of 
      California, San Francisco, CA, USA.
FAU - Deeks, Steven G
AU  - Deeks SG
AUID- ORCID: 0000-0001-6371-747X
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Davidson, Michelle
AU  - Davidson M
AUID- ORCID: 0000-0002-5518-9774
AD  - Department of Medicine, University of California, San Francisco, CA, USA.
FAU - Lu, Scott
AU  - Lu S
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, CA, USA.
FAU - Goldberg, Sarah A
AU  - Goldberg SA
AUID- ORCID: 0000-0002-8642-1468
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, CA, USA.
FAU - Kelly, J Daniel
AU  - Kelly JD
AUID- ORCID: 0000-0002-7616-0321
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, CA, USA.
AD  - F.I. Proctor Foundation, University of California, San Francisco, CA, USA.
FAU - Martin, Jeffrey N
AU  - Martin JN
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, CA, USA.
FAU - Vierra-Green, Cynthia A
AU  - Vierra-Green CA
AD  - CIBMTR (Center for International Blood and Marrow Transplant Research), National 
      Marrow Donor Program/Be The Match, Minneapolis, MN, USA.
FAU - Spellman, Stephen R
AU  - Spellman SR
AD  - CIBMTR (Center for International Blood and Marrow Transplant Research), National 
      Marrow Donor Program/Be The Match, Minneapolis, MN, USA.
FAU - Langton, David J
AU  - Langton DJ
AUID- ORCID: 0000-0003-1178-3031
AD  - ExplantLab, Newcastle-upon-Tyne, UK.
FAU - Dewar-Oldis, Michael J
AU  - Dewar-Oldis MJ
AD  - Department of Biochemistry and Chemistry, La Trobe Institute for Molecular 
      Science, La Trobe University, Bundoora, Victoria, Australia.
FAU - Smith, Corey
AU  - Smith C
AD  - QIMR Berghofer Centre for Immunotherapy and Vaccine Development Brisbane, QIMR 
      Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
FAU - Barnard, Peter J
AU  - Barnard PJ
AUID- ORCID: 0000-0003-1755-7991
AD  - Department of Biochemistry and Chemistry, La Trobe Institute for Molecular 
      Science, La Trobe University, Bundoora, Victoria, Australia.
FAU - Lee, Sulggi
AU  - Lee S
AUID- ORCID: 0000-0003-1560-2250
AD  - Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, 
      University of California, San Francisco, CA, USA.
FAU - Marcus, Gregory M
AU  - Marcus GM
AUID- ORCID: 0000-0001-5197-7696
AD  - Division of Cardiology, Department of Medicine, University of California, San 
      Francisco, CA, USA.
FAU - Olgin, Jeffrey E
AU  - Olgin JE
AD  - Division of Cardiology, Department of Medicine, University of California, San 
      Francisco, CA, USA.
FAU - Pletcher, Mark J
AU  - Pletcher MJ
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, CA, USA.
AD  - Division of General Internal Medicine, University of California, San Francisco, 
      CA, USA.
FAU - Maiers, Martin
AU  - Maiers M
AD  - CIBMTR (Center for International Blood and Marrow Transplant Research), National 
      Marrow Donor Program/Be The Match, Minneapolis, MN, USA.
FAU - Gras, Stephanie
AU  - Gras S
AUID- ORCID: 0000-0001-7416-038X
AD  - Department of Biochemistry and Chemistry, La Trobe Institute for Molecular 
      Science, La Trobe University, Bundoora, Victoria, Australia.
AD  - Department of Biochemistry and Molecular Biology, Biomedicine Discovery 
      Institute, Monash University, Clayton, Victoria, Australia.
FAU - Hollenbach, Jill A
AU  - Hollenbach JA
AUID- ORCID: 0000-0001-6572-7962
AD  - Weill Institute for Neurosciences, Department of Neurology, University of 
      California, San Francisco, CA, USA. jill.hollenbach@ucsf.edu.
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, CA, USA. jill.hollenbach@ucsf.edu.
LA  - eng
GR  - I01 CX002417/CX/CSRD VA/United States
GR  - U24 CA076518/CA/NCI NIH HHS/United States
GR  - UM1 TR004409/TR/NCATS NIH HHS/United States
GR  - L30 AI126521/AI/NIAID NIH HHS/United States
GR  - K23 AI146268/AI/NIAID NIH HHS/United States
GR  - U2C EB021881/EB/NIBIB NIH HHS/United States
GR  - R21 HG012386/HG/NHGRI NIH HHS/United States
GR  - R01 AI159260/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20230719
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Peptides)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 0 (Spike Glycoprotein, Coronavirus)
SB  - IM
UOF - medRxiv. 2022 Oct 12;:. PMID: 34031661
MH  - Humans
MH  - *Alleles
MH  - *Asymptomatic Infections
MH  - *COVID-19/genetics/immunology/physiopathology/virology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Peptides/immunology
MH  - SARS-CoV-2/immunology
MH  - *HLA-B Antigens/immunology
MH  - Cohort Studies
MH  - T-Lymphocytes/immunology
MH  - Immunodominant Epitopes/immunology
MH  - Cross Reactions/immunology
MH  - Spike Glycoprotein, Coronavirus/chemistry/immunology
PMC - PMC10396966
COIS- The authors declare no competing interests.
EDAT- 2023/07/20 01:06
MHDA- 2023/08/04 06:43
PMCR- 2023/07/19
CRDT- 2023/07/19 23:27
PHST- 2022/10/10 00:00 [received]
PHST- 2023/06/15 00:00 [accepted]
PHST- 2023/08/04 06:43 [medline]
PHST- 2023/07/20 01:06 [pubmed]
PHST- 2023/07/19 23:27 [entrez]
PHST- 2023/07/19 00:00 [pmc-release]
AID - 10.1038/s41586-023-06331-x [pii]
AID - 6331 [pii]
AID - 10.1038/s41586-023-06331-x [doi]
PST - ppublish
SO  - Nature. 2023 Aug;620(7972):128-136. doi: 10.1038/s41586-023-06331-x. Epub 2023 
      Jul 19.