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

Elife. 2016 Jan 29;5. pii: e12556. doi: 10.7554/eLife.12556. [Epub ahead of print]

McMurtrey C1, Trolle T2, Sansom T3, Remesh SG4, Kaever T4, Bardet W1, Jackson K1, Nielsen M2, McLeod R5, Zajonc DM4, Blader IJ3, Peters B4, Sette A4, Hildebrand W6.

Author information

Abstract

HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondiiinfected 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. gondiiencoded 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: 

human; immunology; infectious disease; microbiology

PMID:

 

26824387

 

[PubMed - as supplied by publisher]