Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8⁺ T memory cells in convalescent COVID‐19 donors

Clinical & Translational Immunology, Journal Year: 2022, Volume and Issue: 11(10)

Published: Jan. 1, 2022

High-magnitude CD8+ T cell responses are associated with mild COVID-19 disease; however, the underlying characteristics that define cell-mediated protection not well understood. The antigenic breadth and immunodominance hierarchies of epitope-specific cells remain largely unexplored essential for development next-generation broad-protective vaccines. This study identified a broad spectrum conserved SARS-CoV-2 epitopes defined their respective phenotypic profiles following infection.CD8+ from 51 convalescent donors were analysed ability to recognise 133 predicted previously described SARS-CoV-2-derived peptides restricted by 11 common HLA class I allotypes using heterotetramer combinatorial coding, which combined markers allowed in-depth ex vivo profiling at quantitative levels.A comprehensive panel 49 mostly SARS-CoV-2-specific epitopes, including five newly low-magnitude was established. We confirmed HLA-A*01:01/ORF1ab1637-1646 B*07:02/N105-113 B*35:01/N325-333 as third epitope immunodominant features. magnitude subdominant responses, A*03:01/N361-369 A*02:01/S269-277, depended on donors' HLA-I context. All expressed prevalent memory phenotypes, highest frequencies in severe donors.SARS-CoV-2 infection induces predominant response directed against likely contributes long-term disease. observed hierarchy emphasises importance derived nonspike proteins overall protective cross-reactive immune response, could aid future vaccine strategies.

Language: Английский

---

SARS-CoV-2 epitope-specific T cells: Immunity response feature, TCR repertoire characteristics and cross-reactivity

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 10, 2023

The devastating COVID-19 pandemic caused by SARS-CoV-2 and multiple variants or subvariants remains an ongoing global challenge. SARS-CoV-2-specific T cell responses play a critical role in early virus clearance, disease severity control, limiting the viral transmission underpinning vaccine efficacy. Studies estimated broad robust each individual recognized at least 30 to 40 antigen epitopes associated with clinical outcome. Several key immunodominant proteome epitopes, including S protein- non-S protein-derived may primarily induce potent long-lasting antiviral protective effects. In this review, we summarized immune response features of epitope-specific cells targeting different SRAS-CoV-2 structures after infection vaccination, abundance, magnitude, frequency, phenotypic kinetics. Further, analyzed immunodominance hierarchy combination attributes TCR repertoires characteristics, discussed significant implications cross-reactive toward HCoVs, concern, especially Omicron. This review be essential for mapping landscape optimizing current strategy.

Language: Английский

---

Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives

World Journal of Pediatrics, Journal Year: 2024, Volume and Issue: 20(4), P. 307 - 324

Published: Feb. 6, 2024

Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise the pediatric population with debilitating systemic impacts can be fatal at times, meriting further attention from clinicians. Meanwhile, intricate interactions between pathogen virulence factors host defense mechanisms are believed play indispensable roles COVID-19 pathophysiology but remain incompletely understood.

Language: Английский

---

mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses

Journal of Autoimmunity, Journal Year: 2024, Volume and Issue: 144, P. 103175 - 103175

Published: Feb. 21, 2024

SARS-CoV-2-specific CD8

Language: Английский

---

CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 29, 2024

Abstract Influenza B viruses (IBVs) cause substantive morbidity and mortality, yet immunity towards IBVs remains understudied. CD8 + T-cells provide broadly cross-reactive alleviate disease severity by recognizing conserved epitopes. Despite the IBV burden, only 18 IBV-specific T-cell epitopes restricted 5 HLAs have been identified currently. A broader array of is needed to develop effective based vaccines. Here we identify 9 highly HLA-B*07:02, HLA-B*08:01 HLA-B*35:01. Memory tetramer are present within blood tissues. Frequencies decline with age, but maintain a central memory phenotype. HLA-B*07:02 HLA-B*08:01-restricted NP 30-38 epitope-specific distinct receptor repertoires. We structural basis for HLA-B*07:02-restricted NS1 196-206 (11-mer) epitope presentation. Our study increases number epitopes, defines at cellular molecular levels, across tissues age.

Language: Английский

---

The Observed T Cell Receptor Space database enables paired-chain repertoire mining, coherence analysis, and language modeling

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114704 - 114704

Published: Aug. 29, 2024

T cell activation is governed through receptors (TCRs), heterodimers of two sequence-variable chains (often an α and β chain) that synergistically recognize antigen fragments presented on surfaces. Despite this, there only exist repositories dedicated to collecting single-chain, not paired-chain, TCR sequence data. We addressed this gap by creating the Observed Space (OTS) database, a source consistently processed annotated, full-length, paired-chain sequences. Currently, OTS contains 5.35 million redundant (1.63 non-redundant), predominantly human sequences from across 50 studies at least 75 individuals. Using OTS, we identify pairing biases, public TCRs, distinct chain coherence patterns relative antibodies. also release language model, providing paired embedding representations method for residue in-filling conditional partner chain. will be updated as central community resource freely downloadable available web application.

Language: Английский

---

SARS-CoV-2-specific CD8 ⁺ T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(39)

Published: Sept. 16, 2024

Long COVID occurs in a small but important minority of patients following COVID-19, reducing quality life and contributing to healthcare burden. Although research into underlying mechanisms is evolving, immunity understudied. SARS-CoV-2-specific T cell responses are key importance for viral clearance COVID-19 recovery. However, long COVID, the establishment persistence cells far from clear, especially beyond 12 mo postinfection postvaccination. We defined ex vivo antigen-specific B their receptors (TCR) repertoires across 2 y people with COVID. Using 13 SARS-CoV-2 peptide–HLA tetramers, spanning 11 HLA allotypes, as well spike nucleocapsid probes, we tracked CD8 + CD4 B-cells individuals first infection through primary vaccination over 24 mo. The frequencies ORF1a- nucleocapsid-specific remained stable Spike-specific were boosted by vaccination, indicating immunization, fully recovered altered immunodominance hierarchy epitopes. Meanwhile, influenza-specific mo, suggesting no bystander-activation. Compared total populations, enriched central memory phenotype, although proportion decreased acute illness. Importantly, TCR repertoire composition was maintained throughout including postvaccination, postinfection. Overall, understand recall responses, providing insights

Language: Английский

---

Empyemas secondary to ENT infections in children before, during and after the COVID-19 pandemic

Neurochirurgie, Journal Year: 2025, Volume and Issue: unknown, P. 101644 - 101644

Published: Jan. 1, 2025

Language: Английский

---

Molecular determinants of cross-strain influenza A virus recognition by αβ T cell receptors

Science Immunology, Journal Year: 2025, Volume and Issue: 10(104)

Published: Feb. 7, 2025

Cross-reactive αβ T cell receptors (TCRs) recognizing multiple peptide variants can provide effective control of rapidly evolving viruses yet remain understudied. By screening 12 naturally occurring influenza-derived HLA-B*35:01–restricted nucleoprotein (NP) 418–426 epitopes (B*35:01-NP 418 ) that emerged since 1918 within influenza A viruses, including 2024 A/H5N1 we identified functional broadly cross-reactive cells universally NP variants. Binding studies demonstrated TCR cross-reactivity was concomitant with diminished antigen sensitivity. Primary human B*35:01/NP + CD8 lines displayed reduced in the absence coreceptor binding, validating low avidity B*35:01-NP responses. Six TCR–HLA-B*35:01/NP crystal structures showed how TCRs recognized epitope Specific interactions were formed invariant and conserved peptide-HLA features, thus remaining distal from highly varied positions epitope. Our study defines molecular mechanisms associated extensive toward viral relevant to universal protective immunity against influenza.

Language: Английский

---

Age and Latent Cytomegalovirus Infection Do Not Affect the Magnitude of De Novo SARS‐CoV‐2‐Specific CD8⁺ T Cell Responses

European Journal of Immunology, Journal Year: 2025, Volume and Issue: 55(3)

Published: March 1, 2025

ABSTRACT Immunosenescence, age‐related immune dysregulation, reduces immunity upon vaccinations and infections. Cytomegalovirus (CMV) infection results in declining naïve (T ) increasing terminally differentiated emra T cell populations, further aggravating aging. Both immunosenescence CMV have been speculated to hamper the formation of protective T‐cell against novel or emerging pathogens. The SARS‐CoV‐2 pandemic presented a unique opportunity examine impact age and/or on generation de novo SARS‐CoV‐2‐specific CD8 + responses 40 younger (22–40 years) 37 older (50–66 convalescent individuals. Heterotetramer combinatorial coding combined with phenotypic markers were used study 35 epitope‐specific populations directly ex vivo. Neither nor affected frequencies, despite reduced total cells ‐ Robust central memory cm detected adults regardless status. Our data demonstrate that aging status did not response. However, individuals displayed lowest stem scm ), highest PD1 suggesting age, CMV, may long‐term immunity.

Language: Английский

---