title: Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities.
abstract: In all vertebrate animals, CD8(+) cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules. These are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating CTLs. The polymorphism of the MHC effectively individualizes the immune response of each member of the species. We have recently developed efficient methods to generate recombinant human MHC-I (also known as human leukocyte antigen class I, HLA-I) molecules, accompanying peptide-binding assays and predictors, and HLA tetramers for specific CTL staining and manipulation. This has enabled a complete mapping of all HLA-I specificities ("the Human MHC Project"). Here, we demonstrate that these approaches can be applied to other species. We systematically transferred domains of the frequently expressed swine MHC-I molecule, SLA-1*0401, onto a HLA-I molecule (HLA-A*11:01), thereby generating recombinant human/swine chimeric MHC-I molecules as well as the intact SLA-1*0401 molecule. Biochemical peptide-binding assays and positional scanning combinatorial peptide libraries were used to analyze the peptide-binding motifs of these molecules. A pan-specific predictor of peptide-MHC-I binding, NetMHCpan, which was originally developed to cover the binding specificities of all known HLA-I molecules, was successfully used to predict the specificities of the SLA-1*0401 molecule as well as the porcine/human chimeric MHC-I molecules. These data indicate that it is possible to extend the biochemical and bioinformatics tools of the Human MHC Project to other vertebrate species.
authors: Laboratory of Experimental Immunology, University of Copenhagen, Denmark.
authors: Lasse Eggers
authors: LE
authors: Pedersen
authors: Mikkel
authors: M
authors: Harndahl
authors: Michael
authors: M
authors: Rasmussen
authors: Kasper
authors: K
authors: Lamberth
authors: William T
authors: WT
authors: Golde
authors: Ole
authors: O
authors: Lund
authors: Morten
authors: M
authors: Nielsen
authors: Soren
authors: S
authors: Buus
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013552:Swine / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; C438668:swine leukocyte antigen