Structural and dynamic bases underlying enhanced T cell receptor recognition

MHC class I (MHC-I) molecules play a crucial role in immune surveillance by presenting intracellular peptides to CD8+ T lymphocytes via T cell receptors (TCRs).

Recognition of MHC/peptide complexes by TCRs is a critical event in initiation of immune responses toward cancer and viral infections.Financial support from Vetenskapsrådet and Cancerfonden during the last years have allowed us to design a new generation altered peptide ligands that we call super-peptides, that bind with high affinity to MHC-I molecules.

Super-peptides are a powerful and unique tool for improving cancer treatment and vaccines against viral infections.

Their increased immunogenicity induces T cell responses of a magnitude never before observed, and the induced CD8+ T cells cross-react with original peptides, resulting in enhanced responses towards cancer and viral targets.Here we intend to combine X-ray crystallography and NMR analyses to assess the structural and dynamic bases underlying the effects of modified peptides on recognition by CD8 TCRs.

We are in a unique position to perform such studies based on four well-established different peptides and three TCR models.

Besides understanding the possible direct or allosteric effects of the peptide modifications on increased TCR recognition of cancer and viral targets, this study would provide novel insights on pathogen-mediated auto-reactivity. The results from these studies could allow to design novel complementary immunotherapies and/or vaccines.