High-resolution structure of HLA-A*1101 in complex with SARS nucleocapsid peptide

The structure of the human MHC-I molecule HLA-A*1101 in complex with a nonameric peptide (KTFPPTEPK) has been determined by X-ray crystallography to 1.45 Å resolution. The peptide is derived from the SARS-CoV nucleocapsid protein positions 362–370 (SNP_362–370). It is conserved in all known isolates of SARS-CoV and has been verified by in vitro peptide-binding studies to be a good to intermediate binder to HLA-A*0301 and HLA-A*1101, with IC₅₀ values of 70 and 186 nM, respectively [Sylvester-Hvid et al. (2004), Tissue Antigens, 63, 395–400]. In terms of the residues lining the peptide-binding groove, the HLA-A*1101–SNP_362–370 complex is very similar to other known structures of HLA-­A*1101 and HLA-A*6801. The SNP_362–370 peptide is held in place by 17 hydrogen bonds to the α-chain residues and by nine water molecules which are also tightly bound in the peptide-binding groove. Thr6 of the peptide (Thr6p) does not make efficient use of the middle (E) pocket. For vaccine development, there seems to be a potential for optimization targeted at this position. All residues except Thr2p and Lys9p are accessible for T-cell recognition.