title: Repertoire of HLA-DR1-restricted CD4 T-cell responses to capsular Caf1 antigen of Yersinia pestis in human leukocyte antigen transgenic mice.
abstract: Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under development as a recombinant vaccine. However, little is known about the specificity of human T-cell responses for Caf1. We characterized CD4 T-cell epitopes of Caf1 in "humanized" HLA-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T-cell immunity was measured with respect to proliferative and gamma interferon T-cell responses and recognition by a panel of T-cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased toward a single immunodominant epitope near the C terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Musson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ingram
authors.forename: Guillaume
authors.initials: G
authors.lastname: Durand
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ascough
authors.forename: Emma L
authors.initials: EL
authors.lastname: Waters
authors.forename: M Gillian
authors.initials: MG
authors.lastname: Hartley
authors.forename: Timothy
authors.initials: T
authors.lastname: Robson
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillere
authors.forename: E Diane
authors.initials: ED
authors.lastname: Williamson
authors.forename: Shiranee
authors.initials: S
authors.lastname: Sriskandan
authors.forename: Daniel
authors.initials: D
authors.lastname: Altmann
authors.forename: John H
authors.initials: JH
authors.lastname: Robinson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D015798:HLA-DR1 Antigen / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D000939:Epitopes; D006680:HLA Antigens; D015798:HLA-DR1 Antigen; C086725:caf1 protein, Yersinia pestis