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.
【초록키워드】 neutralizing antibody, Antibody Response, Infection, peptide, Spike protein, B cell, cross-reactivity, Epitopes, T cell, Antibody responses, SARS-CoV-2 antibodies, SARS-CoV-2 antibody, peptides, General population, epitope, receptor binding motif, T cell epitope, Neutralizing antibody response, microbial, Support, Post-infection, subject, processing, T cell memory, MHC-II, effective, MHC-II alleles, predicted, lack, develop, evaluated, the spike protein, Examining, raising, RBM, 【제목키워드】 SARS-CoV-2, Analysis, effective, less, RBM,