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 and Daniela Weiskopf ()
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Rimjhim Agarwal: La Jolla Institute for Immunology (LJI)
Calvin Ha: La Jolla Institute for Immunology (LJI)
Fernanda H. Côrtes: La Jolla Institute for Immunology (LJI)
Yeji Lee: La Jolla Institute for Immunology (LJI)
Amparo Martínez-Pérez: La Jolla Institute for Immunology (LJI)
Rosa Isela Gálvez: La Jolla Institute for Immunology (LJI)
Izabella N. Castillo: University of North Carolina School of Medicine
Elizabeth J. Phillips: Murdoch University
Simon A. Mallal: Murdoch University
Angel Balmaseda: Sustainable Sciences Institute
Eva Harris: Berkeley
Claudia M. Romero-Vivas: Fundación Universidad del Norte
Lakshmanane Premkumar: University of North Carolina School of Medicine
Andrew K. Falconar: Fundación Universidad del Norte
Alba Grifoni: La Jolla Institute for Immunology (LJI)
Alessandro Sette: La Jolla Institute for Immunology (LJI)
Daniela Weiskopf: La Jolla Institute for Immunology (LJI)

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-60862-7

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