Identification of equine herpesvirus-1 antigens recognized by cytotoxic T lymphocytes. 2003

Gisela Soboll, and J Millar Whalley, and Mathew T Koen, and George P Allen, and Darrilyn G Fraser, and Michael D Macklin, and William F Swain, and D Paul Lunn
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.

Equine herpesvirus-1 (EHV-1) causes serious disease in horses throughout the world, despite the frequent use of vaccines. CTLs are thought to be critical for protection from primary and reactivating latent EHV-1 infections. However, the antigen-specificity of EHV-1-specific CTLs is unknown. The aim of this study was to identify EHV-1 genes that encode proteins containing CTL epitopes and to determine their MHC I (or ELA-A in the horse) restriction. Equine dendritic cells, transfected with a series of EHV-1 genes, were used to stimulate autologous CTL precursor populations derived from previously infected horses. Cytotoxicity was subsequently measured against EHV-1-infected PWM lymphoblast targets. Dendritic cells were infected with EHV-1 (positive control) or transfected with plasmids encoding the gB, gC, gD, gE, gH, gI, gL, immediate-early (IE) or early protein of EHV-1 using the PowderJect XR-1 research device. Dendritic cells transfected with the IE gene induced CTL responses in four of six ponies. All four of these ponies shared a common ELA-A3.1 haplotype. Dendritic cells transfected with gC, gD, gI and gL glycoproteins induced CTLs in individual ponies. The cytotoxic activity was ELA-A-restricted, as heterologous targets from ELA-A mismatched ponies were not killed and an MHC I blocking antibody reduced EHV-1-specific killing. This is the first identification of an EHV-1 protein containing ELA-A-restricted CTL epitopes. This assay can now be used to study CTL specificity for EHV-1 proteins in horses with a broad range of ELA-A haplotypes, with the goal of developing a multi-epitope EHV-1 vaccine.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D004861 Herpesvirus 1, Equid A species of VARICELLOVIRUS causing abortion and respiratory disease in horses. Equine Herpesvirus 1,Equine abortion Virus,EHV-1,Equid Herpesvirus 1,Herpesvirus 1 (alpha), Equine,Equine abortion Viruses,Herpesvirus 1, Equine
D006566 Herpesviridae Infections Virus diseases caused by the HERPESVIRIDAE. Herpesvirus Infections,B Virus Infection,Infections, Herpesviridae,Infections, Herpesvirus,B Virus Infections,Herpesviridae Infection,Herpesvirus Infection,Infection, B Virus,Infection, Herpesviridae,Infection, Herpesvirus,Infections, B Virus
D006734 Horse Diseases Diseases of domestic and wild horses of the species Equus caballus. Equine Diseases,Disease, Equine,Disease, Horse,Diseases, Equine,Diseases, Horse,Equine Disease,Horse Disease
D006736 Horses Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest. Equus caballus,Equus przewalskii,Horse, Domestic,Domestic Horse,Domestic Horses,Horse,Horses, Domestic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000956 Antigens, Viral Substances elaborated by viruses that have antigenic activity. Viral Antigen,Viral Antigens,Antigen, Viral
D013602 T-Lymphocytes, Cytotoxic Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2. Cell-Mediated Lympholytic Cells,Cytotoxic T Cells,Cytotoxic T Lymphocyte,Cytotoxic T-Lymphocytes,TC1 Cell,TC1 Cells,TC2 Cell,TC2 Cells,Cell Mediated Lympholytic Cells,Cell, Cell-Mediated Lympholytic,Cell, TC1,Cell, TC2,Cell-Mediated Lympholytic Cell,Cytotoxic T Cell,Cytotoxic T Lymphocytes,Cytotoxic T-Lymphocyte,Lymphocyte, Cytotoxic T,Lympholytic Cell, Cell-Mediated,Lympholytic Cells, Cell-Mediated,T Cell, Cytotoxic,T Lymphocyte, Cytotoxic,T Lymphocytes, Cytotoxic,T-Lymphocyte, Cytotoxic

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