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Elife. 2016 Jan 29;5. pii: e12556. doi: 10.7554/eLife.12556.

Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove.

Author information

1
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States.
2
Pure MHC LLC, Austin, United States.
3
Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark.
4
La Jolla Institute for Allergy and Immunology, La Jolla, United States.
5
Department of Microbiology and Immunology, University at Buffalo School of Medicine, Buffalo, United States.
6
University of Chicago, Chicago, United States.
7
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina.

Abstract

HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions.

KEYWORDS:

HLA; T. gondii; crystallography; human; immunology; infectious disease; mass spectrometry; microbiology; peptide ligands

PMID:
26824387
PMCID:
PMC4775218
DOI:
10.7554/eLife.12556
[Indexed for MEDLINE]
Free PMC Article

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