Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4 + T cells in chronic chikungunya disease

Rimjhim Agarwal; Calvin Ha; Fernanda H Côrtes; Yeji Lee; Amparo Martínez-Pérez; Rosa Isela Gálvez; Izabella N Castillo; Elizabeth J Phillips; Simon A Mallal; Angel Balmaseda; Eva Harris; Claudia M Romero-Vivas; Lakshmanane Premkumar; Andrew K Falconar; Alba Grifoni; Alessandro Sette; Daniela Weiskopf

doi:10.1038/s41467-025-60862-7

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Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4 + T cells in chronic chikungunya disease

Journal article

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Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4 + T cells in chronic chikungunya disease

Rimjhim Agarwal, Calvin Ha, Fernanda H Côrtes, Yeji Lee, Amparo Martínez-Pérez, Rosa Isela Gálvez, Izabella N Castillo, Elizabeth J Phillips, Simon A Mallal, Angel Balmaseda, …

Nature communications, Vol.16(1), 5756

2025

DOI: https://doi.org/10.1038/s41467-025-60862-7

PMID: 40592820

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Abstract

CD4-Positive T-Lymphocytes - immunology

Chikungunya Fever - immunology

Chikungunya Fever - virology

Chikungunya virus - genetics

Chikungunya virus - immunology

Chronic Disease

Cross Reactions - immunology

Epitopes, T-Lymphocyte - immunology

Female

Humans

Male

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes acute febrile illness that can progress into chronic arthritis-like disease (CHIKVD) in humans. CD4 T cells have important functions in CHIKV infection, yet the CHIKV target proteins for these CD4 + T cells are poorly characterized. Here, by stimulating PBMCs collected from individuals with chronic CHIKVD with peptides spanning the entire CHIKV proteome, we provide a comprehensive landscape of CHIKV CD4 T cell epitopes. We identify three immunodominant regions and associated core motifs in CHIKV E1, nsP1 and CP proteins. In addition, by in silico assessment of the sequence conservation of CHIKV proteome with closely related alphaviruses, we define CHIKV epitopes conserved across arthritogenic and encephalitic viruses. Overall, our work describes CD4 T cell targets of CHIKV in humans, thereby assisting in studying the functions of CD4 T cells in CHIKV pathogenesis and vaccine design.

Details

Title: Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4 + T cells in chronic chikungunya disease
Authors/Creators: Rimjhim Agarwal - La Jolla Institute for Immunology
Calvin Ha - La Jolla Institute for Immunology
Fernanda H Côrtes - La Jolla Institute for Immunology
Yeji Lee - La Jolla Institute for Immunology
Amparo Martínez-Pérez - La Jolla Institute for Immunology
Rosa Isela Gálvez - La Jolla Institute for Immunology
Izabella N Castillo - University of North Carolina at Chapel Hill
Elizabeth J Phillips - Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Simon A Mallal - Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Angel Balmaseda - Sustainable Sciences Institute
Eva Harris - University of California, Berkeley
Claudia M Romero-Vivas - Universidad del Norte
Lakshmanane Premkumar - University of North Carolina at Chapel Hill
Andrew K Falconar - Universidad del Norte
Alba Grifoni - La Jolla Institute for Immunology
Alessandro Sette - La Jolla Institute for Immunology
Daniela Weiskopf - La Jolla Institute for Immunology
Publication Details: Nature communications, Vol.16(1), 5756
Publisher: Springer Nature
Grant note: 75N93019C00065 / NIAID NIH HHS 75N93024C00056 / NIAID NIH HHS
Identifiers: 991005792773507891
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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