The molecular basis for peptide repertoire selection in the human leucocyte antigen (HLA) C∗06:02 molecule

Abstract

Human leukocyte antigen (HLA)-C∗06:02 is identified as the allele associated with the highest risk for the development of the autoimmune skin disease psoriasis. However, the diversity and mode of peptide presentation by the HLA-C∗06:02 molecule remains unclear. Here, we describe the endogenous peptide repertoire of ∼3,000 sequences for HLA-C∗06:02 that defines the peptide-binding motif for this HLA allomorph. We found that HLA-C∗06:02 predominantly presents nonamer peptides with dominant arginine anchors at the P2 and P7 positions and a preference for small hydrophobic residues at the C terminus (PΩ). To determine the structural basis of this selectivity, we determined crystal structures of ..