Open AccessTuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination
Author(s) -
Adil Doğanay Duru,
Renhua Sun,
Eva B. Allerbring,
Jesseka Chadderton,
Nadir Kadri,
Xiao Han,
Kaliroi Peqini,
Hannes Uchtenhagen,
Chaithanya Madhurantakam,
Sara Pellegrino,
Tatyana Sandalova,
PerÅke Nygren,
Stephen J. Turner,
Adnane Achour
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008244
Subject(s) - t cell receptor , cd8 , cytotoxic t cell , major histocompatibility complex , immune system , biology , peptide , t cell , vaccination , microbiology and biotechnology , immunology , virology , biochemistry , in vitro
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 modification alters the conformations of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, and can be combined with currently available and future vaccination protocols in order to prevent viral immune escape.