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 angstrom resolution. The peptide is derived from the SARS-CoV nucleocapsid protein positions 362 - 370 (SNP362-370). 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 - SNP362 - 370 complex is very similar to other known structures of HLA-A*1101 and HLA-A* 6801. The SNP362-370 peptide is held in place by 17 hydrogen bonds to the alpha-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.