title: Identification of the peptide-binding motif recognized by the pigtail macaque class I MHC molecule Mane-A1*082:01 (Mane A*0301).
abstract: Rhesus and pigtail macaques have proven to be valuable animal models for several important human diseases, including HIV, where they exhibit similar pathology and disease progression. Because rhesus macaques have been extensively characterized in terms of their major histocompatibility complex (MHC) class I alleles, their demand has soared, making them increasingly difficult to obtain for research purposes. This problem has been exacerbated by a continued export ban in place since 1978. Pigtail macaques represent a potential alternative animal model. However, because their MHC class I alleles have not been characterized in detail, their use has been hindered. To address this, in the present study, we have characterized the peptide binding specificity of the pigtail macaque class I allele Mane-A1*082:01 (formerly known as Mane A*0301), representative of the second most common MHC class I antigen detected across several cohorts. The motif was defined on the basis of binding studies utilizing purified MHC protein and panels of single amino acid substitution analog peptides, as well as sequences of peptide ligands eluted from Mane-A1*082:01. Based on these analyses, Mane-A1*082:01 was found to recognize a motif with H in position 2 and the aromatic residues F and Y, or the hydrophobic/aliphatic residue M, at the C-terminus. Finally, analysis of the binding of a combinatorial peptide library allowed the generation of a detailed quantitative motif that proved effective in the prediction of a set of high-affinity binders derived from chimeric SIV/HIV, an important model virus for studying HIV infection in humans.
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Moore
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: A Michelle
authors.initials: AM
authors.lastname: English
authors.forename: Amanda
authors.initials: A
authors.lastname: Wriston
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: Scott
authors.initials: S
authors.lastname: Southwood
authors.forename: Kate
authors.initials: K
authors.lastname: Bradley
authors.forename: Bernard A P
authors.initials: BA
authors.lastname: Lafont
authors.forename: Bianca R
authors.initials: BR
authors.lastname: Mothé
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008254:Macaca nemestrina / Q000276:immunology*; D010455:Peptides / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides