Identification and profiling of HLA-A*02:01-restricted Toxoplasma gondii peptides through immunopeptidomics in HLA-A2.1 transgenic mice.

Authors

Ruiying Liang, Xinru Luo, Weixiang Xia, Haotian Gu, Dan Li, Yongyu Gao, Zonghui Zuo, Fengshan Gao, Jiabo Ding, Xinming Tang, Zibin Li

Published in

Virulence. Volume 17. Issue 1. Pages 2697091. Dec 31, 2026. Epub Jul 05, 2026.

Abstract

HLA class I presentation of pathogen-derived peptides is essential for CD8+ T-cell recognition of Toxoplasma gondii. While in vitro MHC ligands have been documented, the in vivo ligandome during infection progression remains poorly characterized. Here, we employed an MS-based immunopeptidomics approach to directly profile the T. gondii immunopeptidome presented by HLA-A *02:01 in transgenic mice. By employing a hierarchical discovery funnel, our analysis identified a comprehensive repertoire of 3,744 unique T. gondii-derived peptides. Subsequent filtering for canonical 8-12mers, matching the typical binding length for HLA-A *02:01 ligands, established a high-confidence foundational ligandome of 3,433 peptides. Source protein analysis revealed that these peptides originate from diverse parasite proteins, including a substantial proportion of previously uncharacterized hypothetical proteins. Notably, specific ligands were consistently detected across both acute and chronic stages, suggesting stable MHC-I presentation throughout the infection cycle. By integrating in silico predictions with experimental validation, we prioritized 73 high-affinity candidates, five of which exhibited robust HLA-A *02:01 binding capacity in vitro and in vivo. Specifically, we identified a novel ligand derived from glycogen synthase (PGS) and determined its co-crystal structure with HLA-A *02:01, revealing favorable binding architecture. Overall, these findings expand the known HLA-A *02:01-restricted ligand landscape of T. gondii and provide a high-priority list of candidates for future functional validation of CD8+ T-cell immunogenicity.

PMID:
42402043
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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