title: Selection of T-cell epitopes from foot-and-mouth disease virus reflects the binding affinity to different cattle MHC class II molecules.
abstract: The major histocompatibility complex (MHC)-restricted selection of T-cell epitopes of foot-and-mouth disease virus (FMDV) by individual cattle MHC class II DR (BoLA-DR) molecules was studied in a direct MHC-peptide binding assay. By in vitro priming of T lymphocytes derived from animals homozygous for both MHC class I and II, five T-cell epitopes were analyzed in the context of three MHC class II haplotypes. We found that the presentation of these T-cell epitopes was mediated by DR molecules, since blocking this pathway of antigen presentation using monoclonal antibody TH14B completely abolished the proliferative responses against the peptides. To study the DR-restricted presentation of these T-cell epitopes, a direct MHC-peptide binding assay on isolated cattle DR molecules was developed. Purified cattle MHC class II DR molecules of the BoLA-DRB3*0201, BoLA-DRB3*1101, and BoLA-DRB3*1201 alleles were isolated from peripheral blood mononuclear cells. For each allele, one of the identified T-cell epitopes was biotinylated, and used as a marker peptide for the development of a competitive MHC-peptide binding assay. Subsequently, the T-cell epitopes of FMDV with functionally defined MHC class II specificity were analyzed in this binding assay. The affinity of the epitopes to bind to certain DR molecules was significantly correlated to the capacity to induce T-cell proliferation. This demonstrated at the molecular level that the selection of individual T-cell epitopes found at the functional level was indeed the result of MHC restriction.
authors.affiliation: Department of Immunology, Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Haghparast
authors.forename: M H
authors.initials: MH
authors.lastname: Wauben
authors.forename: M C
authors.initials: MC
authors.lastname: Grosfeld-Stulemeyer
authors.forename: P
authors.initials: P
authors.lastname: van Kooten
authors.forename: E J
authors.initials: EJ
authors.lastname: Hensen
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D005537:Aphthovirus / Q000276:immunology*; D001667:Binding, Competitive; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D002417:Cattle; D002460:Cell Line; D006224:Cricetinae; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C442501:VP1 protein, Foot-and-mouth disease virus; C442459:VP2 protein, Foot-and-mouth disease virus; C442460:VP3 protein, Foot-and-mouth disease virus