新型コロナに感染しないワクチン未接種者の”謎” HLA-DQA2 遺伝子の活動レベルの高さと新型コロナへの耐性との間に関連.LoL

Human SARS-CoV-2 challenge uncovers local and systemic response dynamics　Rik G. H. Lindeboom,Kaylee B. Worlock,Lisa M. Dratva,Masahiro Yoshida,David Scobie,
Helen R. Wagstaffe,Laura Richardson,Anna Wilbrey-Clark,Josephine L. Barnes,Lorenz Kretschmer,Krzysztof Polanski,Jessica Allen-Hyttinen,Puja Mehta,Dinithi Sumanaweera,Jacqueline M. Boccacino,Waradon Sungnak,Rasa Elmentaite,Ni Huang,Lira Mamanova,Rakesh Kapuge,Liam Bolt,Elena Prigmore,Ben Killingley,Mariya Kalinova,…Sarah A. Teichmann 
Nature volume 631, pages189–198 (2024)Cite this article
Abstract

The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics of early cellular responses to this disease remains limited1. Here in our SARS-CoV-2 human challenge study, we used single-cell multi-omics profiling of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in seronegative individuals challenged with pre-Alpha SARS-CoV-2. Our analyses revealed rapid changes in cell-type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific time points and infection status. We observed that the interferon response in blood preceded the nasopharyngeal response. Moreover, nasopharyngeal immune infiltration occurred early in samples from individuals with only transient infection and later in samples from individuals with sustained infection. High expression of HLA-DQA2 before inoculation was associated with preventing sustained infection. Ciliated cells showed multiple immune responses and were most permissive for viral replication, whereas nasopharyngeal T cells and macrophages were infected non-productively. We resolved 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our new computational pipeline Cell2TCR identifies activated antigen-responding T cells based on a gene expression signature and clusters these into clonotype groups and motifs. Overall, our detailed time series data can serve as a Rosetta stone for epithelial and immune cell responses and reveals early dynamic responses associated with protection against infection.

https://www.nature.com/articles/s41586-024-07575-x

 

HLA class II histocompatibility antigen, DQ(6) alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leucocyte antigen system.^[5]

The protein encoded by this gene is expressed, but unlike HLA-DQA1, it is apparently unable to heterodimerize with HLA class II beta chain paralogues.^[6] The low level of HLA-DQA2 expression is apparently due to impaired transcription factor binding to the HLA-DQA2 gene promoter.^[7]

ワクチン接種により抗原原罪が発症したらもともとは新型コロナに感染しない人も…

そう言えばワクチン接種開始以前はほとんど新型コロナに感染する人がいなかった国があったような…

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