Nonstandard Peptide Binding Revealed by Crystal Structures of HLA-B5101 Complexed with HIV Immunodominant Epitopes

• Published in: The Journal of immunology (1950) Vol. 165; no. 6; pp. 3260 - 3267
• Main Authors: Maenaka, Katsumi, Maenaka, Taeko, Tomiyama, Hiroko, Takiguchi, Masafumi, Stuart, David I, Jones, E. Yvonne
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-09-2000
• Subjects: Amino Acid Motifs - immunology; Animals; Binding Sites - immunology; Cell Line; Computer Simulation; Cross Reactions; Crystallography, X-Ray; Cytotoxicity Tests, Immunologic; histocompatibility antigen HLA; HIV-1 - chemistry; HIV-1 - immunology; HIV-1 - metabolism; HLA-B Antigens - chemistry; HLA-B Antigens - metabolism; HLA-B51 Antigen; Humans; Immunodominant Epitopes - chemistry; Immunodominant Epitopes - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Macromolecular Substances; Mice; Models, Molecular; Peptide Fragments - chemistry; Peptide Fragments - immunology; Peptide Fragments - metabolism; Protein Binding - immunology; Protein Conformation; Receptors, Immunologic - chemistry; Receptors, Immunologic - metabolism; Receptors, KIR; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.6.3260

The crystal structures of the human MHC class I allele HLA-B*5101 in complex with 8-mer, TAFTIPSI, and 9-mer, LPPVVAKEI, immunodominant peptide epitopes from HIV-1 have been determined by x-ray crystallography. In both complexes, the hydrogen-bonding network in the N-terminal anchor (P1) pocket is rearranged as a result of the replacement of the standard tyrosine with histidine at position 171. This results in a nonstandard positioning of the peptide N terminus, which is recognized by B*5101-restricted T cell clones. Unexpectedly, the P5 peptide residues appear to act as anchors, drawing the peptides unusually deeply into the peptide-binding groove of B51. The unique characteristics of P1 and P5 are likely to be responsible for the zig-zag conformation of the 9-mer peptide and the slow assembly of B*5101. A comparison of the surface characteristics in the alpha1-helix C-terminal region for B51 and other MHC class I alleles highlights mainly electrostatic differences that may be important in determining the specificity of human killer cell Ig-like receptor binding.