CHARACTERISATION OF MHC-PEPTIDE BINDING SPECIFICITIES BY STRUCTURAL STUDIES

Abstract

The human leukocyte antigen (HLA)-C molecules have emerged to have a role in T-cell immunity apart from its dominant role in NK cell recognition. Molecular and structural characterisation of HLA-C molecules has been impeded by its low surface expression and poor assembly. Therefore, a set of refined folding and purification scheme have been developed for HLA-C structural determination. For the first time in 10 years, the crystal structures of 2 novel HLA-C molecules coupled with viral peptides are presented. HLA-C*08:01 is not only able to bind the Cytomegalovirus pp65 peptide (VVCAHELVC) known to elicit a cytotoxic T-cell response but also bind the Influenza matrix peptide (GILGFVFTL) which is HLA-A*02-restricted. The structures, presented at a high resolution of 2.18Å and 1.84Å, allow the examination of HLA-C peptide binding specificities in greater detail and provide a structural basis of HLA-C-peptide complex formation to understand the unique role of HLA-C in immunity.