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

• Published in: PloS one Vol. 16; no. 2; p. e0246731
• Main Authors: Castro, Andrea, Ozturk, Kivilcim, Zanetti, Maurizio, Carter, Hannah
• Format: Journal Article
• Language: English
• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0246731

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.