Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination
Adil Doganay Duru, Renhua Sun, Eva B Allerbring, Jesseka Chadderton, Nadir Kadri, Xiao Han, Kaliroi Peqini, Hannes Uchtenhagen, Chaithanya Madhurantakam, Sara Pellegrino, Tatyana Sandalova, Per-Ake Nygren, Stephen J Turner, Adnane Achour
PLOS PATHOGENS | PUBLIC LIBRARY SCIENCE | Published : 2020
Viral escape from CD8+ cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8+ T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, the p3P ..View full abstract
Awarded by Swedish Research Council
Awarded by Swedish Cancer Society
This work was funded by the Swedish Research Council (2018-02874) and The Swedish Cancer Society CAN (2018/603) to AA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.