Immunome Research
Open Access

Structural bases underlying re-established recognition of a viral immune escape variant

8^th Molecular Immunology and Immunogenetics Congress

March 20-21, 2017 Rome, Italy

Tatyana Sandalova, Allerbring E, Duru AD, Sun R, Han X and Achour A

Karolinska Institutet, Sweden

Posters & Accepted Abstracts: J Immunome Res

Abstract :

MHC-I molecules play a crucial role in immune surveillance by selectively presenting intracellular peptides at the cell surface to CD8+ T lymphocytes, including cytotoxic T lymphocytes, via T cell receptors (TCRs). Recognition of MHC/peptide complexes by TCRs is a critical event in initiation of immune responses. The T cell clone P14 is specific for H-2Db in complex with the Lymphocytic choriomeningitis virus-derived epitope gp33 (KAVYNFATM). The virus escapes immune recognition by modifying peptide position 4 to phenylalanine (Y4F). Using a combination of structural biology and immunology, we have defined a novel procedure that allows for the design of super-peptides that bind with high affinity to MHC-I. This discovery provides a powerful tool for improving vaccination. The highly immunogenic super-peptides act as mimotopes of disease-associated non-immunogenic epitopes. The increased immunogenicity induces T cell responses of a magnitude never before observed and our results demonstrate that the induced CD8+ T cells cross-react with the original peptides, resulting in enhanced in vitro and in vivo responses. Here we present for the first time the crystal structure of P14 in complex with H-2Db bound to five different peptides, providing a structural basis for our methodology. All five ternary structures revealed virtually the same TCR interface and contacts with an average RMSD of 0.45 �?�?. Both the V�?± and V�?² domains of P14 contribute equally to the interaction with H-2Db. In contrast to many others, no contacts are formed between CDR2�?± and H-2Db. Instead, several contacts are formed between the CDR3�?± residues several H-2Db residues. Three residues of gp33, pY4, pF6 and pT8 interact with CDR3�?². R97�?² located at the tip of CDR3�?² interacts with both bulky residues of peptide, pY4 and pF6, and pT8 interacts with D93�?².

Biography :

Dr. Sandalova (PhD in Biophysics) has expertise in protein crystallography and modeling of three-dimensional structure. Her results have been published in 70 papers. Dr.Sandalova has contributed more than 100 protein structures to the Protein Data Bank.

Email: Tatyana.Sandalova@ki.se