Characterization of Conserved and Promiscuous Human Rhinovirus CD4 T Cell Epitopes.

Marta Gomez-Perosanz,Esther M Lafuente,Pedro A Reche,John Sidney,Miguel Fernandez-Arquero,Tara Fiyouzi,Ellis L Reinherz,Alessandro Sette

doi:10.3390/cells10092294

Marta Gomez-Perosanz, Esther M Lafuente + Show 6 more

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https://doi.org/10.3390/cells10092294

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Abstract

Human rhinovirus (RV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from RV A and 8 from RV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in RV A and C serotypes and predicted to bind to multiple human leukocyte antigen class II (HLA II) molecules. We found positive T cell recall responses by interferon gamma (IFNγ)-ELISPOT assays to eight peptides, validating seven of them (three from RV A and four from RV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these seven epitopes could be recognized by >95% of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor RV infections and to develop peptide-based vaccines against most RV A and C serotypes.

Highlights

Accepted: 31 August 2021Human rhinovirus (RV) species A and C are the most frequent cause of viral respiratory tract infections worldwide [1]
It has been established that RV C species are the main cause of acute exacerbations in individuals with underlying chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, or asthma [3]
We considered a response to a peptide as positive if, after subtracting the mean ± standard deviation of the background control, the mean of detected IFNγ-SFC was at least 60 SFC/106 peripheral blood mononuclear cells (PBMCs)

Summary

Introduction

Human rhinovirus (RV) species A and C are the most frequent cause of viral respiratory tract infections worldwide [1]. RV infections are relatively mild and self-limited to the upper respiratory tract, being the most common cause of the common cold. In those patients with chronic respiratory diseases, in particular children and immunocompromised individuals, RVs can infect the lower respiratory tract, causing severe symptoms of bronchiolitis and pneumonia [2]. It has been established that RV C species are the main cause of acute exacerbations in individuals with underlying chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, or asthma [3]. There is no vaccine for RV, and understating the immune response to RV is a necessary step

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