Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients.

Dong, T.; Peng, Y.; Mentzer, A. J.; Liu, G.; Yao, X.; Yin, Z.; Dong, D.; Dejnirattisai, W.; Turtle, L.; Rostron, T.; Subramaniam, K.; Thomson, P.; Zhang, P.; Dold, C.; Ratcliff, J.; de Silva, T.; Sopp, P.; Wellington, D.; Rajapaksa, U.; Paes, W.; Borrow, P.; Kessler, B. M.; Fry, J. W.; Schwabe, N. F.; Semple, M. G.; Baillie, J. K.; Openshaw, P. J.; Cornall, R. J.; Conlon, C.; Screaton, G.; Klenerman, P.; Mongkolsapaya, J.; McMichael, A.; Knight, J. C.; Ogg, G.; Simmonds, P.; Lockett, T.; Levin, R.; Moore, S. C.; Salio, M.; Napolitani, G.; Chen, Y.-L.; Dunachie, S.; Supasa, P.; Liu, C.; Lopez-C

doi:10.1101/2020.06.05.134551

Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.06.05.134551

Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients.

View original source ↗Export metadata ↓

Abstract

COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFN{gamma} based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 were significantly higher in severe compared to mild COVID-19 cases, and this effect was most marked in response to spike, membrane, and ORF3a proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti-Nucleoprotein (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4+ and/or CD8+ epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M, 32%, 47%) and one in the nucleoprotein (Np, 35%). CD8+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8+ T cells than spike-specific CD8+ T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8+ to CD4+ T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non-spike proteins within future COVID-19 vaccine design.

Source connections

Published article ↗

Explore related subjects

immunology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Dong, T., Peng, Y., Mentzer, A. J., Liu, G., Yao, X., Yin, Z., Dong, D., Dejnirattisai, W., Turtle, L., Rostron, T., Subramaniam, K., Thomson, P., Zhang, P., Dold, C., Ratcliff, J., de Silva, T., Sopp, P., Wellington, D., Rajapaksa, U., Paes, W., Borrow, P., Kessler, B. M., Fry, J. W., Schwabe, N. F., Semple, M. G., Baillie, J. K., Openshaw, P. J., Cornall, R. J., Conlon, C., Screaton, G., Klenerman, P., Mongkolsapaya, J., McMichael, A., Knight, J. C., Ogg, G., Simmonds, P., Lockett, T., Levin, R., Moore, S. C., Salio, M., Napolitani, G., Chen, Y.-L., Dunachie, S., Supasa, P., Liu, C., Lopez-C. 2020-06-08. Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients.. https://doi.org/10.1101/2020.06.05.134551

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Proteome-wide discovery of novel diagnostic antigens for coccidioidomycosis

Coccidioidomycosis, commonly called Valley Fever (VF), caused by Coccidioides spp., is an understudied fungal disease that accounts for a substantial fraction of pneumonias in endemic areas. Diagnosis remains challenging because the mainstay of diagnosis is serology, and current assays have modest sensitivity in early infection. Discovery of new antigens could improve serologic detection early in disease. Here, we use PepSeq, a DNA-programmable serology platform, to represent the complete proteome of Coccidioides within a library of 244,000 DNA-barcoded peptides. By profiling antibody reactivity at the protein and epitope levels in VF patients, naturally infected pigtail macaques, and healthy controls, we identify numerous previously-unrecognized antigens and epitopes, including some shared between humans and macaque responses. When translated into a pooled peptide ELISA, we show that a subset of identified antigens can discriminate VF cases from controls in an independent cohort with high accuracy (AUC = 0.91). These findings establish high-dimensional peptide serology as a scalable approach for fungal antigen discovery and identify new targets for improved VF diagnosis.

immunology↗

bioRxiv2026

Establishing an ex vivo platform for molecular profiling of skin structural cells using frozen human skin biopsies

Skin structural cells, including keratinocytes, melanocytes, endothelial cells, and fibroblasts, play critical roles in the development of chronic inflammatory skin disease. Inflammatory stimuli induce transcriptional reprogramming and epigenetic changes in skin structural cells, which contribute to disease pathogenesis. Although two-dimensional (2D) and three-dimensional (3D) skin culture models have been widely used to investigate inflammatory responses in skin structural cells, ex vivo systems that maintain skin structure and cellular composition remain limited. To address this gap, we explored using frozen skin biopsies as an experimental platform to study the responses of skin structural cells to inflammatory stimuli. Using a simple air-liquid interface culture method on permeable Transwell inserts, we showed that viable skin structural cells that retain cell-type-specific transcriptional profiles can be recovered from frozen skin biopsies after prolonged in vitro culture. Stimulation with IFN-{gamma} induced robust transcriptional and chromatin accessibility changes that were largely resolved after stimulus removal, with transcriptional responses to secondary stimulation comparable to the primary stimulation. Treatment of cultured skin biopsies with histone-modifying enzyme inhibitors effectively altered global histone modification levels, but did not substantially affect the transcriptional resolution of IFN-{gamma}-induced responses. Collectively, these findings establish cryopreserved human skin biopsies as a scalable ex vivo platform that enables mechanistic studies of inflammatory responses of multiple populations of skin structural cells.

immunology↗

bioRxiv2026

γδ T cell-derived IL-17A aggravates experimental epidermolysis bullosa acquisita in response to IL-1β

Epidermolysis bullosa acquisita (EBA) is a mucocutaneous autoimmune blistering disorder mediated by autoantibodies against type VII collagen and subsequent splitting of the dermal-epidermal junction. Interleukin (IL)-17A promotes the production of chemokines and cytokines involved in neutrophil recruitment and activation, suggesting that IL-17A may contribute to EBA pathogenesis. We aimed to clarify the role of IL-17A in experimental EBA. Using an antibody transfer-induced EBA mouse model, we demonstrate that IL-17A promotes disease development, as pharmacological blockade of IL-17A with a neutralizing antibody ameliorated skin lesions. Gamma-delta ({gamma}{delta}) T cells were identified as the predominant cellular source of IL-17A, supported by the attenuated disease phenotype observed in {gamma}{delta}TCR-deficient mice. In addition, CD4+ T cells and neutrophils contributed to IL-17A production in experimental EBA. Mechanistically, IL-1-beta, rather than IL-23, was identified as a critical mediator of IL-17A production by {gamma}{delta} T cells in vitro, consistent with our in vivo findings. Whereas EBA severity was not reduced in IL-23p19-deficient mice, disease was markedly attenuated in IL-1R-deficient animals. Together, our study provides the first evidence that {gamma}{delta} T cell-derived IL-17A plays a pivotal role in experimental EBA and identifies a previously unrecognized IL-1{beta}/{gamma}{delta} T cell/IL-17A axis that expands current understanding of EBA immunopathogenesis.

immunology↗