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      Immunodominance complexity: lessons yet to be learned from dominant T cell responses to SARS- COV-2

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          Abstract

          Immunodominance is a complex and highly debated topic of T cell biology. The current SARS-CoV-2 pandemic has provided the opportunity to profile adaptive immune responses and determine molecular factors contributing to emerging responses towards immunodominant viral epitopes. Here, we discuss parameters that alter the dynamics of CD8 viral epitope processing, generation and T-cell responses, and how immunodominance counteracts viral immune escape mechanisms that develop in the context of emerging SARS-CoV-2 variants.

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          Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

          Alba Grifoni, Daniela Weiskopf, Sydney Ramirez … (2020)
          Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.
          Article 0 comments Cited 1968 times – based on 0 reviews     Review now
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            Coronavirus biology and replication: implications for SARS-CoV-2

            Philip V’kovski, Annika Kratzel, Silvio Steiner … (2020)
            The SARS-CoV-2 pandemic and its unprecedented global societal and economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into the human population. Although the previous coronavirus SARS-CoV and MERS-CoV epidemics raised awareness of the need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. The development of effective intervention strategies relies on the knowledge of molecular and cellular mechanisms of coronavirus infections, which highlights the significance of studying virus–host interactions at the molecular level to identify targets for antiviral intervention and to elucidate critical viral and host determinants that are decisive for the development of severe disease. In this Review, we summarize the first discoveries that shape our current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle and relate that to our knowledge of coronavirus biology. The elucidation of similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness and strategies to combat coronavirus infections.
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              Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

              Yanchun Peng, Alexander Mentzer, Guihai Liu … (2020)
              The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.
              Article 0 comments Cited 644 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Curr Opin Virol
                Journal ID (iso-abbrev): Curr Opin Virol
                Title: Current Opinion in Virology
                Publisher: Published by Elsevier B.V.
                ISSN (Print): 1879-6257
                ISSN (Electronic): 1879-6265
                Publication date PMC-release: 8 September 2021
                Publication date (Electronic): 8 September 2021
                Affiliations
                [1 ]MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford University, Oxford OX3 9DS, UK
                [2 ]Chinese Academy of Medical Sciences (CAMS) Oxford Institute, Nuffield Department of Medicine, Oxford University, Oxford OX3 7BN, UK
                [3 ]Target Discovery Institute, Nuffield Department of Medicine, Oxford University, Oxford OX3 7BN, UK
                Article
                Publisher Item ID: S1879-6257(21)00096-1
                DOI: 10.1016/j.coviro.2021.08.009
                PMC ID: 8424056
                PubMed ID: 34534732
                SO-VID: 11f3629f-3f47-482b-8c02-f429a519182e
                Copyright © © 2021 Published by Elsevier B.V.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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