부산대학교 도서관

The structural determination of peptide: HLA (human leucocyte antigen) class I complexes by X-ray crystallography has provided valuable information for understanding how peptides bind to individual HLA class I molecules and how this may influence the immune response. We compared 101 crystal structures of 9-mer peptide: HLA class I complexes available in the protein data bank ( PDB) by performing a contact analysis using the Contact Map Analysis webserver http://ligin.weizmann.ac.il/cma. An InterSystems Caché 'post-relational' database containing residue position, amino acid (AA) and buried surface that contact a particular peptide position was then created allowing data comparison for all the structures ( Pocketcheck). The analysis illustrates that the HLA class I residues 24, 45, 63 and 67 show high contact frequencies to both the p1 and/or p2 position of bound peptides, indicating that they might influence the nature of a peptide anchor. To determine the influence of these residues we utilized soluble HLA technology and mass spectrometry to analyze peptides derived from HLA-B*44:06 since it differs from the previously described allele B*44:02 by seven AA exchanges located in the alpha 1 domain (residues 24, 32, 41, 45, 63, 67 and 80). HLA-B*44:06 features an anchor motif of P or A at p2 and Y or W at the C-terminal. Additionally B*44:06-derived peptides feature an auxiliary anchor motif at p1, comprising D or E. Our results illustrate that structural analysis can provide valuable information to understand allogenicity and provides a further step towards intelligent HLA mismatching. [ABSTRACT FROM AUTHOR]