title: Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C.
abstract: Rhinovirus (RV) species A and C are the most frequent cause of respiratory viral illness worldwide, and RV-C has been linked to more severe exacerbations of asthma in young children. Little is known about the immune responses to the different RV species, although studies comparing IgG1 antibody titers found impaired antibody responses to RV-C. Therefore, the aim of this study was to assess whether T-cell immunity to RV-C is similarly impaired. We measured T-cell proliferation to overlapping synthetic peptides covering the entire VP1 capsid protein of an RV-A and RV-C genotype for 20 healthy adult donors. Human leukocyte antigen (HLA) was typed in all the donors in order to investigate possible associations between the HLA type and RV peptide recognition. Total and specific IgG1 antibody titers to the VP1 proteins of both RV-A and RV-C were also measured to examine associations between the antibody and T-cell responses. We identified T-cell epitopes that are specific to and representative of each RV-A and RV-C species. These epitopes stimulated CD4+-specific T-cell proliferation, with similar magnitudes of response for both RV species. All the donors, independent of their HLA-DR or -DQ type, were able to recognize the immunodominant RV-A and -C regions of VP1. Furthermore, the presence or absence of specific antibody titers was not related to changes in T-cell recognition. Our results indicate a dissociation between the antibody and T-cell responses to rhinoviruses. The species-representative T-cell epitopes identified in this study are valuable tools for future studies investigating T-cell responses to the different RV species.
  
  
  OBJECTIVE
  Rhinoviruses (RVs) are mostly associated with the common cold and asthma exacerbations, although their contributions to most upper and lower respiratory tract diseases have increasingly been reported. Species C (RV-C) has been associated with more frequent and severe asthma exacerbations in young children and, along with RV-A, is the most clinically relevant species. Little is known about how our immune system responds to rhinoviruses, and there are limited tools to study specific adaptive immunity against each rhinovirus species. In this study, we identified immunodominant T-cell epitopes of the VP1 proteins of RV-A and RV-C, which are representative of each species. The study found that T-cell responses to RV-A and RV-C were of similar magnitudes, in contrast with previous findings showing RV-C-specific antibody responses were low. These findings will provide the basis for future studies on the immune response to rhinoviruses and can help elucidate the mechanisms of severity of rhinovirus-induced infections.
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.|School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: Cibele M
authors.initials: CM
authors.lastname: Gaido
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: Shane
authors.initials: S
authors.lastname: Stone
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors.forename: Abha
authors.initials: A
authors.lastname: Chopra
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Thomas
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.|Princess Margaret Hospital for Children, Perth, Australia.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Le Souëf
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia belinda.hales@telethonkids.org.au.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Hales
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood; D000918:Antibody Specificity; D001249:Asthma / Q000209:etiology / Q000276:immunology; D003139:Common Cold / Q000150:complications / Q000276:immunology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D064368:Healthy Volunteers; D006650:Histocompatibility Testing; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012229:Rhinovirus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D014764:Viral Proteins; C074995:viral protein 1, rhinovirus