Viral T cell epitope mapping and immunodominance: experimental and computational advances

T cells are central to antiviral immunity, contributing to viral clearance, long-term immune memory, and protection against reinfection. Over the past decade, advances in high-throughput peptide screening, immunopeptidomics, single-cell profiling, and computational prediction have greatly expanded the ability to identify viral CD8⁺ and CD4⁺ T cell epitopes presented by MHC class I and class II molecules. These approaches are reshaping how antiviral T cell responses are mapped across acute, chronic, emerging, and re-emerging viral infections.Despite this progress, major challenges remain. For many clinically relevant viruses, experimentally validated T cell epitope repertoires are still incomplete, and discrepancies frequently persist between predicted and validated epitopes. Important questions also remain regarding immunodominance, HLA restriction, population coverage, cross-reactivity, and the effects of viral evolution on epitope conservation and immune recognition. A more integrative framework is therefore needed to move beyond epitope cataloguing toward a deeper understanding of how viral epitopes are processed, presented, prioritized, and altered across diverse host and viral contexts.The goal of this Research Topic is to address key conceptual and technical challenges in the identification, validation, and interpretation of viral T cell epitopes. In particular, this collection aims to bring together studies that integrate experimental immunology — including optimized peptide-pool design, immunopeptidomics, functional T cell assays, single-cell approaches, and high-dimensional phenotyping — with advanced computational methods such as machine learning-based epitope prediction, peptide-HLA binding models, and TCR-peptide-HLA interaction modelling.By spanning in vitro systems, ex vivo human samples, relevant animal models, and in silico frameworks, this Topic seeks to clarify the determinants of antigen processing, presentation, immunodominance, population-level variability, and immune escape. Ultimately, these insights will support next-generation vaccine design, improved immune monitoring across genetically diverse populations, and better preparedness against evolving viral threats.We welcome Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to:• experimental and computational identification and validation of viral CD8⁺ and CD4⁺ T cell epitopes;• high-throughput epitope mapping strategies, including peptide-pool design, pool optimization, deconvolution methods, and immunopeptidomics;• functional and phenotypic characterization of epitope-specific T cells, including cytokine production, cytotoxicity, polyfunctionality, memory, and exhaustion states;• determinants of immunodominance, antigen processing and presentation, HLA restriction, epitope conservation, and population coverage;• population-level variability in T cell responses across diverse genetic and HLA backgrounds;cross-reactivity, viral evolution, immune escape, and the stability of T cell recognition across viral variants and related viruses;translational applications of viral T cell epitope mapping in vaccine design, immune monitoring, and antiviral immunotherapies.Contributions may address any viral pathogen — including acute, chronic, emerging, and re-emerging viruses — and may leverage human cohorts, relevant animal models, or in silico approaches. Studies that integrate experimental and computational frameworks are particularly encouraged. Topic editors: Syed Faraz Ahmed, Muhammad Saqib Sohail, Anne M Hahn Source: https://www.frontiersin.org/research-topics/80753/viral-t-cell-epitope-mapping-and-immunodominance-experimental-and-computational-advances