ArticleEmerging microbes & infections2023
HLA-Bw4 in association with KIR3DL1 favors natural killer cell-mediated protection against severe COVID-19.
Article in Emerging microbes & infections, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- SARS-CoV-2 ORF8: an accessory protein at the interface of immune evasion and inflammation.Frontiers in immunology · 2026Review
- Expanding the Genetic Framework: Insights into Non-HLA-B27 Contributions to Axial Spondylarthritis.Medicina (Kaunas, Lithuania) · 2025Article
- Post-translational modification of NK cell receptors offers clues to antigenic specificity riddle.Frontiers in immunology · 2025Review
- Association of KIR Genes with Middle East Respiratory Syndrome Coronavirus Infection in South Koreans.Journal of clinical medicine · 2024Article
- Challenges of CRISPR/Cas-Based Cell Therapy for Type 1 Diabetes: How Not to Engineer a "Trojan Horse".International journal of molecular sciences · 2023Review
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replicating SARS-CoV-2 has been shown to degrade HLA class I on target cells to evade the cytotoxic T-cell (CTL) response. HLA-I downregulation can be sensed by NK cells to unleash killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition by the cognate HLA-I ligands. Here, we investigated the impact of HLA and KIR genotypes and HLA-KIR combinations on COVID-19 outcome. We found that the peptide affinities of HLA alleles were not correlated with COVID-19 severity. The predicted poor binders for SARS-CoV-2 peptides belong to HLA-B subtypes that encode KIR ligands, including Bw4 and C1 (introduced by B*46:01), which have a small F pocket and cannot accommodate SARS-CoV-2 CTL epitopes. However, HLA-Bw4 weak binders were beneficial for COVID-19 outcome, and individuals lacking the HLA-Bw4 motif were at higher risk for serious illness from COVID-19. The presence of the HLA-Bw4 and KIR3DL1 combination had a 58.8% lower risk of developing severe COVID-19 (OR = 0.412, 95% CI = 0.187-0.904,
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