PMID- 27630239 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20220318 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 90 IP - 23 DP - 2016 Dec 1 TI - Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C. PG - 10459-10471 LID - 10.1128/JVI.01701-16 [doi] AB - 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. IMPORTANCE: 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. CI - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved. FAU - Gaido, Cibele M AU - Gaido CM AD - Telethon Kids Institute, University of Western Australia, Perth, Australia. AD - School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. FAU - Stone, Shane AU - Stone S AD - Telethon Kids Institute, University of Western Australia, Perth, Australia. FAU - Chopra, Abha AU - Chopra A AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia. FAU - Thomas, Wayne R AU - Thomas WR AD - Telethon Kids Institute, University of Western Australia, Perth, Australia. FAU - Le Souef, Peter N AU - Le Souef PN AD - School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. AD - Princess Margaret Hospital for Children, Perth, Australia. FAU - Hales, Belinda J AU - Hales BJ AD - Telethon Kids Institute, University of Western Australia, Perth, Australia belinda.hales@telethonkids.org.au. LA - eng PT - Journal Article DEP - 20161114 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antibodies, Viral) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Immunodominant Epitopes) RN - 0 (Viral Proteins) RN - 0 (viral protein 1, rhinovirus) SB - IM MH - Adult MH - Amino Acid Sequence MH - Antibodies, Viral/blood MH - Antibody Specificity MH - Asthma/etiology/immunology MH - Common Cold/complications/immunology/virology MH - Epitopes, T-Lymphocyte/genetics/*immunology MH - Female MH - Healthy Volunteers MH - Histocompatibility Testing MH - Humans MH - Immunodominant Epitopes/genetics/*immunology MH - Lymphocyte Activation MH - Male MH - Middle Aged MH - Rhinovirus/classification/genetics/*immunology MH - Sequence Homology, Amino Acid MH - Species Specificity MH - T-Lymphocytes/immunology MH - Viral Proteins/genetics/*immunology MH - Young Adult PMC - PMC5110196 EDAT- 2016/09/16 06:00 MHDA- 2017/05/16 06:00 PMCR- 2017/05/14 CRDT- 2016/09/16 06:00 PHST- 2016/08/25 00:00 [received] PHST- 2016/09/04 00:00 [accepted] PHST- 2016/09/16 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/09/16 06:00 [entrez] PHST- 2017/05/14 00:00 [pmc-release] AID - JVI.01701-16 [pii] AID - 01701-16 [pii] AID - 10.1128/JVI.01701-16 [doi] PST - epublish SO - J Virol. 2016 Nov 14;90(23):10459-10471. doi: 10.1128/JVI.01701-16. Print 2016 Dec 1.