HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype.
CD4 counts
CITE-seq
HLA
KIR
NK cells
RNA-seq
Thailand
acute HIV infection
cytotoxic T lymphocytes
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
10 08 2022
10 08 2022
Historique:
received:
30
11
2021
revised:
17
01
2022
accepted:
09
06
2022
pubmed:
17
7
2022
medline:
16
8
2022
entrez:
16
7
2022
Statut:
ppublish
Résumé
Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia.
Identifiants
pubmed: 35841889
pii: S1931-3128(22)00310-9
doi: 10.1016/j.chom.2022.06.005
pmc: PMC9380401
mid: NIHMS1817876
pii:
doi:
Substances chimiques
Epitopes
0
HLA-B Antigens
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1173-1185.e8Subventions
Organisme : NIAID NIH HHS
ID : AAI20052001
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068635
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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