Comprehensive mapping of human CD4+ T cell epitopes for Nipah and measles as prototype Paramyxoviruses

Alison Tarke; Mariah Macias; Claudia Francisco Morales; Tanner Michaelis; Leila Siddiqui; Esther Dawen Yu; Raphael Trevizani; Abril Zuniga; Christian Zmasek; Elizabeth Phillips; Simon Mallal; Brandon Lin; Jesus O Estevez; Jonathan R Erlich; Nicole V Johnson; Jason S McLellan; April Frazier; Ricardo da Silva Antunes; Gene S Tan; Alba Grifoni; Alessandro Sette

doi:10.1016/j.xcrm.2026.102838

Comprehensive mapping of human CD4⁺ T cell epitopes for Nipah and measles as prototype Paramyxoviruses

Cell Rep Med. 2026 Jun 2:102838. doi: 10.1016/j.xcrm.2026.102838. Online ahead of print.

Authors

Alison Tarke¹, Mariah Macias¹, Claudia Francisco Morales¹, Tanner Michaelis¹, Leila Siddiqui¹, Esther Dawen Yu¹, Raphael Trevizani², Abril Zuniga³, Christian Zmasek³, Elizabeth Phillips⁴, Simon Mallal⁴, Brandon Lin³, Jesus O Estevez³, Jonathan R Erlich³, Nicole V Johnson⁵, Jason S McLellan⁵, April Frazier¹, Ricardo da Silva Antunes¹, Gene S Tan⁶, Alba Grifoni¹, Alessandro Sette⁷

Affiliations

¹ Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
² Oswaldo Cruz Foundation, São José, S/N - Precabura, Eusébio, CE 61773-270, Brazil.
³ Department of Informatics, J. Craig Venter Institute, La Jolla, CA 92037, USA.
⁴ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA WA 6150, Australia.
⁵ Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
⁶ Department of Informatics, J. Craig Venter Institute, La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
⁷ Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. Electronic address: alex@lji.org.

PMID: 42229425
DOI: 10.1016/j.xcrm.2026.102838

Abstract

Paramyxoviruses comprise a diverse family of viruses that threaten global human health through direct infection and zoonotic transmission. Understanding adaptive immune responses to these viruses is critical for characterizing host-pathogen interactions and evaluating vaccine performance. Here, we systematically map human CD4⁺ T cell epitopes across Nipah and measles viruses, two prototypic members of the Paramyxoviridae family. We identify broad epitope repertoires, including 186 Nipah and 288 measles epitopes recognized in multiple donors. Epitopes are characterized for HLA binding and inferred restrictions, and broader HLA binding correlates with immunodominance. We observe overlapping T cell targets between viruses, with N and F proteins immunodominant in both and L additionally dominant in Nipah. We define conserved T cell epitope regions (CTERs) in Nipah virus that encompass 17% of the proteome, capture over 50% of T cell responses, show high conservation across different Henipaviruses, and elicit broadly cross-reactivity, supporting broad population coverage.

Keywords: CTER; Nipah; Paramyxovirus; T cells; epitopes; immunogenic regions; measles; pandemic preparedness; sequence conservation; vaccine.