Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisation
SARS-CoV-2 has claimed more than 7 million lives worldwide and has been associated with prolonged inflammation, immune dysregulation and persistence of symptoms following severe infection. Understanding the T cell mediated immune response and factors impacting development and continuity of SARS-CoV-...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549570/full |
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| author | Gavin Markey Joseph McLaughlin Joseph McLaughlin Darren McDaid Seodhna M. Lynch Andrew English Andrew English H. Denis Alexander Martin Kelly Manav Bhavsar Victoria McGilligan Shu-Dong Zhang Elaine K. Murray Taranjit Singh Rai Colum Walsh Colum Walsh Anthony J. Bjourson Priyank Shukla David S. Gibson |
| author_facet | Gavin Markey Joseph McLaughlin Joseph McLaughlin Darren McDaid Seodhna M. Lynch Andrew English Andrew English H. Denis Alexander Martin Kelly Manav Bhavsar Victoria McGilligan Shu-Dong Zhang Elaine K. Murray Taranjit Singh Rai Colum Walsh Colum Walsh Anthony J. Bjourson Priyank Shukla David S. Gibson |
| author_sort | Gavin Markey |
| collection | DOAJ |
| description | SARS-CoV-2 has claimed more than 7 million lives worldwide and has been associated with prolonged inflammation, immune dysregulation and persistence of symptoms following severe infection. Understanding the T cell mediated immune response and factors impacting development and continuity of SARS-CoV-2 specific memory T cells is pivotal for developing better therapeutic and monitoring strategies for those most at risk from COVID-19. Here we present a comprehensive analysis of memory T cells in a convalescent cohort (n=20), three months post Omicron infection. Utilising flow cytometry to investigate CD4+CD45RO+ and CD8+CD45RO+ memory T cell IL-2 expression following Omicron (B.1.1.529/BA.1) peptide pool stimulation, alongside T cell receptor repertoire profiling and RNA-Seq analysis, we have identified several immunological features associated with hospitalised status. We observed that while there was no significant difference in median CD4+CD45RO+ IL-2+ and CD8+ CD45RO+ IL-2+ memory T cell count between subgroups, the hospitalised subgroup expressed significantly more IL-2 per cell following Omicron peptide pool exposure in the CD8+CD45RO+ population (p <0.03) and trended towards significance in CD4+CD45RO+ cells (p <0.06). T cell receptor repertoire analysis found that the non-hospitalised subgroup had a much higher number of circulating clonotypes, targeting a wider range of predominantly MHC-I epitopes across the SARS-CoV-2 genome. Several immunodominant epitopes, conserved between both subgroups, were observed, however hospitalised individuals were less likely to express putative HLA alleles responsible for pMHC presentation which may impact TCR affinity. We observed a bias towards shorter CDR3 segments in TCRβ repertoire analysis within the hospitalised subgroup, alongside lower rates of repertoire overlap in CDR3 sequences compared to the non-hospitalised subgroup. We found a significant proportion of TCRs targeted epitopes along the SARS-CoV-2 genome including non-structural proteins, responsible for viral replication and immune evasion. These findings highlight how the continuity of T cell based protective immunity is impacted by both the viral replication cycle of SARS-CoV-2 upon intracellular and innate immune responses, and HLA-type upon TCR affinity and clonotype formation. Our novel Epitope Target Analysis Pipeline (Epi-TAP) could prove beneficial in development of new therapeutic strategies through rapid identification of shared immunodominant epitopes across non-hospitalised and hospitalised subgroups. |
| format | Article |
| id | doaj-art-9566cc9d8a3447619d2d61a5bef50f15 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-9566cc9d8a3447619d2d61a5bef50f152025-08-20T01:51:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15495701549570Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisationGavin Markey0Joseph McLaughlin1Joseph McLaughlin2Darren McDaid3Seodhna M. Lynch4Andrew English5Andrew English6H. Denis Alexander7Martin Kelly8Manav Bhavsar9Victoria McGilligan10Shu-Dong Zhang11Elaine K. Murray12Taranjit Singh Rai13Colum Walsh14Colum Walsh15Anthony J. Bjourson16Priyank Shukla17David S. Gibson18Personalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomMedical Directorate, Clinical and Translational Research and Innovation Centre, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomSchool of Health and Life Sciences, Teesside University, Middlesborough, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomIntensive Care Unit, Western Health Social Care Trust, Londonderry, United KingdomIntensive Care Unit, Western Health Social Care Trust, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomGenomic Medicine Research Group, School of Biomedical Science, Ulster University, Coleraine, United KingdomBiomedical and Clinical Sciences Division, Department for Cell and Neurobiology, Faculty of Medicine, Linköping University, Linköping, SwedenPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomPersonalised Medicine Centre, School of Medicine, Ulster University, Londonderry, United KingdomSARS-CoV-2 has claimed more than 7 million lives worldwide and has been associated with prolonged inflammation, immune dysregulation and persistence of symptoms following severe infection. Understanding the T cell mediated immune response and factors impacting development and continuity of SARS-CoV-2 specific memory T cells is pivotal for developing better therapeutic and monitoring strategies for those most at risk from COVID-19. Here we present a comprehensive analysis of memory T cells in a convalescent cohort (n=20), three months post Omicron infection. Utilising flow cytometry to investigate CD4+CD45RO+ and CD8+CD45RO+ memory T cell IL-2 expression following Omicron (B.1.1.529/BA.1) peptide pool stimulation, alongside T cell receptor repertoire profiling and RNA-Seq analysis, we have identified several immunological features associated with hospitalised status. We observed that while there was no significant difference in median CD4+CD45RO+ IL-2+ and CD8+ CD45RO+ IL-2+ memory T cell count between subgroups, the hospitalised subgroup expressed significantly more IL-2 per cell following Omicron peptide pool exposure in the CD8+CD45RO+ population (p <0.03) and trended towards significance in CD4+CD45RO+ cells (p <0.06). T cell receptor repertoire analysis found that the non-hospitalised subgroup had a much higher number of circulating clonotypes, targeting a wider range of predominantly MHC-I epitopes across the SARS-CoV-2 genome. Several immunodominant epitopes, conserved between both subgroups, were observed, however hospitalised individuals were less likely to express putative HLA alleles responsible for pMHC presentation which may impact TCR affinity. We observed a bias towards shorter CDR3 segments in TCRβ repertoire analysis within the hospitalised subgroup, alongside lower rates of repertoire overlap in CDR3 sequences compared to the non-hospitalised subgroup. We found a significant proportion of TCRs targeted epitopes along the SARS-CoV-2 genome including non-structural proteins, responsible for viral replication and immune evasion. These findings highlight how the continuity of T cell based protective immunity is impacted by both the viral replication cycle of SARS-CoV-2 upon intracellular and innate immune responses, and HLA-type upon TCR affinity and clonotype formation. Our novel Epitope Target Analysis Pipeline (Epi-TAP) could prove beneficial in development of new therapeutic strategies through rapid identification of shared immunodominant epitopes across non-hospitalised and hospitalised subgroups.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549570/fullSARS-CoV-2COVID-19T cell immunityT cell receptor (TCR) recognitionantigen presentationadaptive immunity |
| spellingShingle | Gavin Markey Joseph McLaughlin Joseph McLaughlin Darren McDaid Seodhna M. Lynch Andrew English Andrew English H. Denis Alexander Martin Kelly Manav Bhavsar Victoria McGilligan Shu-Dong Zhang Elaine K. Murray Taranjit Singh Rai Colum Walsh Colum Walsh Anthony J. Bjourson Priyank Shukla David S. Gibson Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisation Frontiers in Immunology SARS-CoV-2 COVID-19 T cell immunity T cell receptor (TCR) recognition antigen presentation adaptive immunity |
| title | Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisation |
| title_full | Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisation |
| title_fullStr | Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisation |
| title_full_unstemmed | Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisation |
| title_short | Distinct Omicron longitudinal memory T cell profile and T cell receptor repertoire associated with COVID-19 hospitalisation |
| title_sort | distinct omicron longitudinal memory t cell profile and t cell receptor repertoire associated with covid 19 hospitalisation |
| topic | SARS-CoV-2 COVID-19 T cell immunity T cell receptor (TCR) recognition antigen presentation adaptive immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549570/full |
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