RT Journal Article
SR Electronic
T1 Crystal Structures of Two Closely Related but Antigenically Distinct HLA-A2/Melanocyte-Melanoma Tumor-Antigen Peptide Complexes
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 3276
OP 3284
DO 10.4049/jimmunol.167.6.3276
VO 167
IS 6
A1 Sliz, Piotr
A1 Michielin, Olivier
A1 Cerottini, Jean-Charles
A1 Luescher, Immanuel
A1 Romero, Pedro
A1 Karplus, Martin
A1 Wiley, Don C.
YR 2001
UL http://www.jimmunol.org/content/167/6/3276.abstract
AB We have determined high-resolution crystal structures of the complexes of HLA-A2 molecules with two modified immunodominant peptides from the melanoma tumor-associated protein Melan-A/Melanoma Ag recognized by T cells-1. The two peptides, a decamer and nonamer with overlapping sequences (ELAGIGILTV and ALGIGILTV), are modified in the second residue to increase their affinity for HLA-A2. The modified decamer is more immunogenic than the natural peptide and a candidate for peptide-based melanoma immunotherapy. The crystal structures at 1.8 and 2.15 Å resolution define the differences in binding modes of the modified peptides, including different clusters of water molecules that appear to stabilize the peptide-HLA interaction. The structures suggest both how the wild-type peptides would bind and how three categories of cytotoxic T lymphocytes with differing fine specificity might recognize the two peptides.