Journal article

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

Abstract

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 ..

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University of Melbourne Researchers