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A SARS-CoV-2 NSP7 homolog of a Treg epitope suppresses CD4+ and CD8+ T cell memory responses

Title: A SARS-CoV-2 NSP7 homolog of a Treg epitope suppresses CD4+ and CD8+ T cell memory responses
Authors: Miah, S. M. Shahjahan; Lelias, Sandra; Gutierrez, Andres H.; McAllister, Mitchell; Boyle, Christine M.; Moise, Lenny; De Groot, Anne S.
Source: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224
Publisher Information: Frontiers Media SA
Publication Year: 2023
Collection: Frontiers (Publisher - via CrossRef)
Description: Pathogens escape host defenses by T-cell epitope mutation or deletion (immune escape) and by simulating the appearance of human T cell epitopes (immune camouflage). We identified a highly conserved, human-like T cell epitope in non-structural protein 7 (NSP7) of SARS-CoV-2, RNA-dependent RNA polymerase (RdRp) hetero-tetramer complex. Remarkably, this T cell epitope has significant homology to a T regulatory cell epitope (Tregitope) previously identified in the Fc region of human immunoglobulin G (IgG) (Tregitope 289). We hypothesized that the SARS-CoV-2 NSP7 epitope (NSP7-289) may induce suppressive responses by engaging and activating pre-existing regulatory T cells. We therefore compared NSP7-289 and IgG Tregitopes (289 and 289z, a shorter version of 289 that isolates the shared NSP7 epitope) in vitro . Tregitope peptides 289, 289z and NSP7-289 bound to multiple HLA-DRB1 alleles in vitro and suppressed CD4+ and CD8+ T cell memory responses. Identification and in vitro validation of SARS-CoV-2 NSP7-289 provides further evidence of immune camouflage and suggests that pathogens can use human-like epitopes to evade immune response and potentially enhance host tolerance. Further exploration of the role of cross-conserved Tregs in human immune responses to pathogens such as SARS-CoV-2 is warranted.
Document Type: article in journal/newspaper
Language: unknown
DOI: 10.3389/fimmu.2023.1290688
DOI: 10.3389/fimmu.2023.1290688/full
Availability: https://doi.org/10.3389/fimmu.2023.1290688; https://www.frontiersin.org/articles/10.3389/fimmu.2023.1290688/full
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.B1C87476
Database: BASE