title: Molecular determinants of peptide binding to two common rhesus macaque major histocompatibility complex class II molecules.
abstract: Major histocompatibility complex class II molecules encoded by two common rhesus macaque alleles Mamu-DRB1*0406 and Mamu-DRB*w201 have been purified, and quantitative binding assays have been established. The structural requirements for peptide binding to each molecule were characterized by testing panels of single-substitution analogs of the two previously defined epitopes HIV Env242 (Mamu-DRB1*0406 restricted) and HIV Env482 (Mamu-DRB*w201 restricted). Anchor positions of both macaque DR molecules were spaced following a position 1 (P1), P4, P6, P7, and P9 pattern. The specific binding motif associated with each molecule was distinct, but largely overlapping, and was based on crucial roles of aromatic and/or hydrophobic residues at P1, P6, and P9. Based on these results, a tentative Mamu class II DR supermotif was defined. This pattern is remarkably similar to a previously defined human HLA-DR supermotif. Similarities in binding motifs between human HLA and macaque Mamu-DR molecules were further illustrated by testing a panel of more than 60 different single-substitution analogs of the HLA-DR-restricted HA 307-319 epitope for binding to Mamu-DRB*w201 and HLA-DRB1*0101. The Mamu-DRB1*0406 and -DRB*w201 binding capacity of a set of 311 overlapping peptides spanning the entire simian immunodeficiency virus (SIV) genome was also evaluated. Ten peptides capable of binding both molecules were identified, together with 19 DRB1*0406 and 43 DRB*w201 selective binders. The Mamu-DR supermotif was found to be present in about 75% of the good binders and in 50% of peptides binding with intermediate affinity but only in approximately 25% of the peptides which did not bind either Mamu class II molecule. Finally, using flow cytometric detection of antigen-induced intracellular gamma interferon, we identify a new CD4(+) T-lymphocyte epitope encoded within the Rev protein of SIV.
authors.affiliation: Epimmune, Inc., San Diego, California 92121, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Dzuris
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.forename: H
authors.initials: H
authors.lastname: Horton
authors.forename: R
authors.initials: R
authors.lastname: Correa
authors.forename: D
authors.initials: D
authors.lastname: Carter
authors.forename: R W
authors.initials: RW
authors.lastname: Chesnut
authors.forename: D I
authors.initials: DI
authors.lastname: Watkins
authors.forename: A
authors.initials: A
authors.lastname: Sette
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D006678:HIV / Q000276:immunology; D006684:HLA-DR Antigens / Q000737:chemistry / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D008253:Macaca mulatta / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments; D014759:Viral Envelope Proteins