ArticlePLoS pathogens2021
Cross-reactive and mono-reactive SARS-CoV-2 CD4+ T cells in prepandemic and COVID-19 convalescent individuals.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- A systemic review of T-cell epitopes defined from the proteome of SARS-CoV-2.Virus research · 2023Pooled it
- Serial vaccination expands and refines human CD4bioRxiv : the preprint server for biology · 2026Article
- Identification of immunodominant T cell epitopes in SARS-CoV-2 spike protein in Syrian hamsters.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Cut or bind? Antigen-specific processing mechanisms define CD4Genome medicine · 2025Article
- Aging and Viral Evolution Impair Immunity Against Dominant Pan-Coronavirus-Reactive T Cell Epitope.European journal of immunology · 2025Article
- Article
- A tentative exploration for the association between influenza virus infection and SARS-CoV-2 infection in Shihezi, China: A test-negative study.Infectious Disease Modelling · 2025Article
- Lack of memory recall in human CD4 T cells elicited by the first encounter with SARS-CoV-2.iScience · 2024Article
- The Influence of Cross-Reactive T Cells in COVID-19.Biomedicines · 2024Review
- Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8Nature immunology · 2024Article
- High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4Frontiers in immunology · 2024Article
- Immunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T-cell epitopes specific to seasonal coronaviruses or cross-reactive with SARS-CoV-2.PLoS pathogens · 2023Article
- Targets and cross-reactivity of human T cell recognition of common cold coronaviruses.Cell reports. Medicine · 2023Article
- Article
- Targets and cross-reactivity of human T cell recognition of Common Cold Coronaviruses.bioRxiv : the preprint server for biology · 2023Article
- SARS-CoV-2 epitope-specific T cells: Immunity response feature, TCR repertoire characteristics and cross-reactivity.Frontiers in immunology · 2023Review
- Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4Frontiers in immunology · 2023Article
- Immunopeptidome profiling of human coronavirus OC43-infected cells identifies CD4 T cell epitopes specific to seasonal coronaviruses or cross-reactive with SARS-CoV-2.bioRxiv : the preprint server for biology · 2022Article
- The immune response as a double-edged sword: The lesson learnt during the COVID-19 pandemic.Immunology · 2022Review
- SARS-CoV-2-specific T cells in unexposed adults display broad trafficking potential and cross-react with commensal antigens.Science immunology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Class II tetramer reagents for eleven common DR alleles and a DP allele prevalent in the world population were used to identify SARS-CoV-2 CD4+ T cell epitopes. A total of 112, 28 and 42 epitopes specific for Spike, Membrane and Nucleocapsid, respectively, with defined HLA-restriction were identified. Direct ex vivo staining of PBMC with tetramer reagents was used to define immunodominant and subdominant T cell epitopes and estimate the frequencies of these T cells in SARS-CoV-2 exposed and naïve individuals. Majority of SARS-CoV-2 epitopes identified have <67% amino acid sequence identity with endemic coronaviruses and are unlikely to elicit high avidity cross-reactive T cell responses. Four SARS-CoV-2 Spike reactive epitopes, including a DPB1*04:01 restricted epitope, with ≥67% amino acid sequence identity to endemic coronavirus were identified. SARS-CoV-2 T cell lines for three of these epitopes elicited cross-reactive T cell responses to endemic cold viruses. An endemic coronavirus Spike T cell line showed cross-reactivity to the fourth SARS-CoV-2 epitope. Three of the Spike cross-reactive epitopes were subdominant epitopes, while the DPB1*04:01 restricted epitope was a dominant epitope. Frequency analyses showed Spike cross-reactive T cells as detected by tetramers were present at relatively low frequency in unexposed people and only contributed a small proportion of the overall Spike-specific CD4+ T cells in COVID-19 convalescent individuals. In total, these results suggested a very limited number of SARS-CoV-2 T cells as detected by tetramers are capable of recognizing ccCoV with relative high avidity and vice versa. The potentially supportive role of these high avidity cross-reactive T cells in protective immunity against SARS-CoV-2 needs further studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.