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?:abstract
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SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.
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?:creator
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?:doi
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?:doi
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10.1101/2020.12.26.424449
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?:journal
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?:license
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?:pdf_json_files
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document_parses/pdf_json/1a0589ddde98e5fd0890df4ad7875b3c14d066de.json; document_parses/pdf_json/bea8890d299534fcc02cb7d67d8d02d6d713e828.json
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?:pmc_json_files
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document_parses/pmc_json/PMC7781323.xml.json
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?:pmcid
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?:pmid
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?:pmid
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?:publication_isRelatedTo_Disease
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?:sha_id
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?:source
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BioRxiv; Medline; PMC; WHO
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?:title
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MHC-II constrains the natural neutralizing antibody response to the SARS-CoV-2 spike RBM in humans
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?:type
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?:year
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