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In silico analysis suggests less effective MHC-II presentation of SARS-CoV-2 RBM peptides: Implication for neutralizing antibody responses.
Castro, Andrea; Ozturk, Kivilcim; Zanetti, Maurizio; Carter, Hannah.
  • Castro A; Biomedical Informatics Program, University of California San Diego, La Jolla, CA, United States of America.
  • Ozturk K; Division of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America.
  • Zanetti M; Division of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America.
  • Carter H; The Laboratory of Immunology, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America.
PLoS One ; 16(2): e0246731, 2021.
Article in English | MEDLINE | ID: covidwho-1079371
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Histocompatibility Antigens Class II / Epitopes, B-Lymphocyte / Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Journal.pone.0246731

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Histocompatibility Antigens Class II / Epitopes, B-Lymphocyte / Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Journal.pone.0246731