In silico analysis suggests less effective MHC-II presentation of SARS-CoV-2 RBM peptides: Implication for neutralizing antibody responses

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 respo...

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Published inPloS one Vol. 16; no. 2; p. e0246731
Main Authors Castro, Andrea, Ozturk, Kivilcim, Zanetti, Maurizio, Carter, Hannah
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 11.02.2021
Public Library of Science (PLoS)
Subjects
ACE2
Amino Acid Motifs
Amino acids
Angiotensin-converting enzyme 2
Antibodies
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Antibody Formation
Antigenic drift
Antigens
Asymptomatic
B-Lymphocytes - immunology
Binding proteins
Bioinformatics
Biology and Life Sciences
Cancer
CD4 antigen
Computer programs
Computer Simulation
Cooperation
Coronaviruses
COVID-19
COVID-19 - immunology
Data analysis
Disease transmission
Drafting software
Editing
Epitopes
Epitopes, B-Lymphocyte - chemistry
Epitopes, B-Lymphocyte - immunology
Funding
Genetics
Health aspects
Histocompatibility Antigens Class II - immunology
Humans
Immunology
Infections
Influenza
Influenza A
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Medicine
Medicine and Health Sciences
MHC antibodies
Models, Molecular
Peptides
Peptides - chemistry
Peptides - immunology
Proteins
Reviews
SARS-CoV-2 - chemistry
SARS-CoV-2 - immunology
Seroconversion
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Software
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - immunology
T-Lymphocytes - immunology
Viral diseases
Viral infections
Viruses
Visualization
United States
La Jolla California
United States > US
Online AccessGet full text
ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0246731

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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.
AbstractList 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.
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.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.
About the Authors: Andrea Castro Roles Data curation, Formal analysis, Software, Validation, Visualization, Writing – original draft, Writing – review & editing Affiliations Biomedical Informatics Program, University of California San Diego, La Jolla, CA, United States of America, Division of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America ORCID logo https://orcid.org/0000-0002-5873-2496 Kivilcim Ozturk Roles Data curation, Formal analysis, Software, Validation, Visualization, Writing – original draft Affiliation: Division of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America Maurizio Zanetti Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing * E-mail: mzanetti@health.ucsd.edu (MZ); hkcarter@health.ucsd.edu (HC) Affiliations The Laboratory of Immunology, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States of America Hannah Carter Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing * E-mail: mzanetti@health.ucsd.edu (MZ); hkcarter@health.ucsd.edu (HC) Affiliations Division of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States of America Introduction Upon infection with SARS-CoV-2 the individual undergoes seroconversion. In the influenza A virus (PR8) system it was shown that while Th1 CD4 T cell responses on their own are ineffective at promoting recovery from infection, antibodies generated through T-B cooperation were indispensable in the protective response against the virus [36]. In a different influenza A strain, it was shown that T-B cooperation and CD4 T cells represent a limiting factor in the kinetics and early magnitude of the primary B cell response to virus challenge and provide help in a preferential way (i.e. intra-molecular but nor inter-molecular) [37]. ACE2 interface is resistant to antigenic drift. [...]we may refer to this site as a key RBM B cell epitope in the generation of potent NAbs.
Audience Academic
Author Carter, Hannah
Castro, Andrea
Ozturk, Kivilcim
Zanetti, Maurizio
AuthorAffiliation 4 Moores Cancer Center, University of California San Diego, La Jolla, CA, United States of America
2 Division of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America
Translational Health Science & Technology Institute, INDIA
3 The Laboratory of Immunology, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America
1 Biomedical Informatics Program, University of California San Diego, La Jolla, CA, United States of America
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crossref_primary_10_3390_vaccines10020191
crossref_primary_10_1371_journal_ppat_1010260
crossref_primary_10_3390_vaccines12040342
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2021 Castro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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– notice: 2021 Castro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Competing Interests: The authors have declared that no competing interests exist.
ORCID 0000-0002-5873-2496
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Snippet SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will...
About the Authors: Andrea Castro Roles Data curation, Formal analysis, Software, Validation, Visualization, Writing – original draft, Writing – review &...
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SubjectTerms ACE2
Amino Acid Motifs
Amino acids
Angiotensin-converting enzyme 2
Antibodies
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Antibody Formation
Antigenic drift
Antigens
Asymptomatic
B-Lymphocytes - immunology
Binding proteins
Bioinformatics
Biology and Life Sciences
Cancer
CD4 antigen
Computer programs
Computer Simulation
Cooperation
Coronaviruses
COVID-19
COVID-19 - immunology
Data analysis
Disease transmission
Drafting software
Editing
Epitopes
Epitopes, B-Lymphocyte - chemistry
Epitopes, B-Lymphocyte - immunology
Funding
Genetics
Health aspects
Histocompatibility Antigens Class II - immunology
Humans
Immunology
Infections
Influenza
Influenza A
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Medicine
Medicine and Health Sciences
MHC antibodies
Models, Molecular
Peptides
Peptides - chemistry
Peptides - immunology
Proteins
Reviews
SARS-CoV-2 - chemistry
SARS-CoV-2 - immunology
Seroconversion
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Software
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - immunology
T-Lymphocytes - immunology
Viral diseases
Viral infections
Viruses
Visualization
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Title In silico analysis suggests less effective MHC-II presentation of SARS-CoV-2 RBM peptides: Implication for neutralizing antibody responses
URI https://www.ncbi.nlm.nih.gov/pubmed/33571241
https://www.proquest.com/docview/2488535110
https://www.proquest.com/docview/2489271224
https://pubmed.ncbi.nlm.nih.gov/PMC7877779
https://doaj.org/article/ce0e3836379441bfb0710cbfe2de3791
http://dx.doi.org/10.1371/journal.pone.0246731
Volume 16
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