Structural and physical properties of the Hepatitis C Virus (HCV) 1406 TCR and NS31406‐1415/HLA‐A2 pMHC complexes

Abstract

In the human body, the adaptive immune system provides a highly specialized pathway to eliminate and prevent pathogen growth. The glycoproteins encoded by the major histocompatibility complex (MHC) are located on the outer membrane of antigen presenting cells, or APCs. MHC proteins are used to display peptide antigens to T cells. In the case of MHC class I molecules, peptides are derived from cytosolic proteins, including virally produced proteins that are present in an infected cell. Previous work described the presence of HLA‐A2‐restricted; HCV‐NS31406 specific T cells in an HLA‐A2 negative transplant recipient who received an HLA‐A2 positive HCV infected liver. This is a unique immunological opportunity, as the patient's T cells could not be positively selected on an HLA‐A2 ligand. Such “allospecific” T cells are exceedingly rare, and by some theories of T cell development, should not even exist. We aim to characterize this unusual TCR‐pMHC interaction, which may possess features distinct from more common interactions that have been used to develop the “rules” of TCR‐pMHC engagement. Here, circular dichroism and differential scanning fluorimetry were utilized to study the stability of NS3/HLA‐A2 ligands. Surface plasmon resonance was used to investigate TCR‐pMHC binding, and preliminary work towards a structure of the complex is shown.