Cut or bind? Antigen-specific processing mechanisms define CD4+ T cell immunodominant epitopes for SARS-CoV-2 S and N proteins
We establish a scalable, genomics-informed framework for decoding CD4⁺ T cell immunodominance across diverse HLA contexts. Our findings reveal that antigen-intrinsic features govern the preferential processing pathway - FCtb for Spike and FBtc for Nucleocapsid - and validate the utility of minimal peptide pools for population-level immune-monitoring. These insights inform the design of personalized immunotherapies and broadly effective vaccines.
Authors
- Jana Sticht (ORCID: https://orcid.org/0000-0002-4307-4726)
- Monika C. Brunner‐Weinzierl (ORCID: https://orcid.org/0000-0002-6838-3568)
- Christian Freund (ORCID: https://orcid.org/0000-0001-7416-8226)
- Frank Kuppler
- Holger Lingel (ORCID: https://orcid.org/0000-0002-3407-8610)
- Esam T. Abualrous (ORCID: https://orcid.org/0000-0001-9582-9089)
- Cecilia Clementi (ORCID: https://orcid.org/0000-0001-9221-2358)
- Benno Kuropka (ORCID: https://orcid.org/0000-0001-5088-6346)
- Miguel Álvaro‐Benito (ORCID: https://orcid.org/0000-0002-6019-3567)
- Stefan Meltendorf (ORCID: https://orcid.org/0000-0002-9555-596X)
- Jakob Holzapfel
- Paula de Diego Valera
Institutions
- Ain Shams University (EG)
- Universidad Complutense de Madrid (ES)
- Research Institute Hospital 12 de Octubre (ES)
- Freie Universität Berlin (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- Genome Medicine
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1186/s13073-025-01577-8
- Primary Topic
- vaccines and immunoinformatics approaches
- Type
- article
- Field-Weighted Citation Impact
- 0.00