Studentship: MDV-specific T cell responses
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by Marek’s disease virus (MDV) or Gallid herpesvirus 2. The life cycle of MDV in chickens constitutes inhalation of cell-free MDV by chickens, followed by transfer of the virus from lungs to lymphoid tissues. Within lymphoid tissues, the virus proceeds to a cytolytic phase in B cells, which is then followed by latent and neoplastic phases in T cells resulting in clinical manifestations. Productive infection, which leads to the release of infectious virus particles, occurs in feather follicles.
Immunity against MD is dependent on interactions between innate and acquired immune mechanisms. Among the acquired mechanisms, T cells play an important role in immunity. Cytotoxic CD8+ T lymphocytes (CTL) are induced in the course of MDV infection and CTL responses are targeted towards infected host cells that express MDV antigens, such as meq and pp38. CTL responses may be an important contributing factor in genetic resistance to MD, perhaps by preventing reactivation of MDV from the latent phase in resistant and not in susceptible chickens. The proposed research project investigates host-pathogen interactions, particularly T cell-mediated immune response to MDV in chickens. In this project, we aim to identify CD8+ T cell epitopes within MDV-encoded proteins such as meq, and pp38 and analyse the functional abilities of these MDV specific CD8+ T cells in resistant and susceptible chicken lines. In brief, the results from this proposal will provide tools to identify-MDV specific CD8+ T cells in chicken and establish whether there is any association between genetic resistance to the infection and the quantity/ quality of MDV specific CD8+ T cell responses.
Immunity against MD is dependent on interactions between innate and acquired immune mechanisms. Among the acquired mechanisms, T cells play an important role in immunity. Cytotoxic CD8+ T lymphocytes (CTL) are induced in the course of MDV infection and CTL responses are targeted towards infected host cells that express MDV antigens, such as meq and pp38. CTL responses may be an important contributing factor in genetic resistance to MD, perhaps by preventing reactivation of MDV from the latent phase in resistant and not in susceptible chickens. The proposed research project investigates host-pathogen interactions, particularly T cell-mediated immune response to MDV in chickens. In this project, we aim to identify CD8+ T cell epitopes within MDV-encoded proteins such as meq, and pp38 and analyse the functional abilities of these MDV specific CD8+ T cells in resistant and susceptible chicken lines. In brief, the results from this proposal will provide tools to identify-MDV specific CD8+ T cells in chicken and establish whether there is any association between genetic resistance to the infection and the quantity/ quality of MDV specific CD8+ T cell responses.
Planned Impact
unavailable
People |
ORCID iD |
| Shahriar Behboudi (Principal Investigator) |
Publications
Adams JRG
(2023)
Preventing bacterial disease in poultry in the post-antibiotic era: a case for innate immunity modulation as an alternative to antibiotic use.
in Frontiers in immunology
Boodhoo N
(2021)
Differential Virus-Specific IFN-Gamma Producing T Cell Responses to Marek's Disease Virus in Chickens With B19 and B21 MHC Haplotypes.
in Frontiers in immunology
Boodhoo N
(2022)
Marek's disease virus-specific T cells proliferate, express antiviral cytokines but have impaired degranulation response.
in Frontiers in immunology
Boodhoo N
(2016)
1a,25(OH)2 Vitamin D3 Modulates Avian T Lymphocyte Functions without Inducing CTL Unresponsiveness.
in PloS one
Boodhoo N
(2016)
Marek's disease in chickens: a review with focus on immunology.
in Veterinary research
Boodhoo N
(2022)
Corrigendum: Marek's disease virus-specific T cells proliferate, express antiviral cytokines but have impaired degranulation response.
in Frontiers in immunology
Kamble N
(2021)
Marek's Disease Virus Modulates T Cell Proliferation via Activation of Cyclooxygenase 2-Dependent Prostaglandin E2.
in Frontiers in immunology
| Description | Through the research funded on this grant, we have developed novel methods and assays for analyzing cell-mediated immune responses in chickens. These methods and assays helped us to identify T cell epitopes within Marek's Disease Virus, an important viral infections in chicken. The knowledge obtained from this project will help us design better vaccines against poultry viral infections. The information obtained from this project provide information on the role of nutrient on the function of immune system cells and their effects on immune responses to Marek's Disease. |
| Exploitation Route | The immunological methods developed here could be used by other researchers and industry to assess antigen specific immune responses in chickens in response to different vaccines or vaccination strategies. |
| Sectors | Agriculture Food and Drink |
| Title | Developed assays for evaluation of antigen specific memory chicken T cells |
| Description | An in vitro model for generation of effector cells from memory T cells for chicken T cells were developed |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | This method will enable scientists working on poultry vaccines and immune response to pathogens to assess memory T cell responses in chickens. |
| Title | Development of assay for assessing antigen-specific T cell responses in chickens |
| Description | An in vitro assay were developed to generate effector memory T cells from memory T cells (cultured ELISPOT assay for chicken T cells) |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | Enables scientists to assess memory T cell responses induced by poultry vaccines |
| Title | Development of chicken NKT cell tetramer |
| Description | Tetramer for detection and quantification of chicken NKT cells are developed and tested. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | This will lead to identification of a novel chicken lymphocytes which has major role in the control of infectious diseases and tumour in chickens. |
| Title | Generation of cell-free virus using feather follicle stem cells |
| Description | An in vitro model for generation and purification of cell-free virus using feather follicule stem cells |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2020 |
| Provided To Others? | No |
| Impact | Cell lines could be used to generate cell free vaccines against Marek's disease virus |
| Description | Professor Jim Kaufman |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Provided information on CD4 T cell epitopes derived from Marek's disease virus |
| Collaborator Contribution | Provided knowledge and information on assessing peptide binding to chicken MHC molecules |
| Impact | Generation of data leading to understanding correlate of protection against Marek's disease virus. |
| Start Year | 2019 |
| Description | Professor Shayan Sharif, University of Guelph, Canada |
| Organisation | University of Guelph |
| Department | Department of Pathobiology |
| Country | Canada |
| Sector | Academic/University |
| PI Contribution | Collaboration between my team and Professor Sharif lead to new finding in Avian immunology, specifically in understanding the effects of nutrients on antigen presenting cells and T cells of chicken. We took the lead in studying the effects of some nutrients (Vitamin D) on the function of chicken T cells, performed most of the experiments in our laboratory. Meanwhile, we participated in studying the effects of Vitamin D on antigen presenting cells of chicken by performing some key experiments because we had access to some specific reagents (monoclonal antibodies) recognizing molecules expressed on chicken antigen presenting cells. |
| Collaborator Contribution | Professor Sharif team took the lead in studying the effects of Vitamin D on antigen presenting cells of chicken, and contributed to experimental plan for studying the effects on chicken T cells. |
| Impact | Two publications in 2015 and 2016: 1. Nitish Boodhoo, Shayan Sharif, Shahriar Behboudi. 1a,25(OH)2 Vitamin D3 Modulates Avian T Lymphocyte Functions without Inducing CTL Unresponsiveness. PLoS One. 2016 Feb 24;11(2):e0150134 2. Bahram Shojadoost, Shahriar Behboudi, Villanueva AI, Jennifer Brisbin, Ali Ashkar, Shayan Sharif. Vitamin D3 modulates the function of chicken macrophages. Res. Vet. Sci. 2015 June, 100: 45-51 |
| Start Year | 2019 |
| Description | Ash Manor school challenge week science workshops |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Discussion of research activities with school children and the school reported increased interests in the related subject. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Big Bang Fair |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | This is a South of England Showground in which students from schools and their parents participated which lead to discussion and interest in both school children and their parents. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://nearme.thebigbangfair.co.uk/view/?eve_id=1956 |
| Description | Diamond open day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Over 300 people visited our stand at the open day, in which we described the importance of our work for food security and public health. Children from all ages were involved and learned about viruses and played with the huge virus particle that we had produced. One of the major impact was that we described to several people why we work on some viruses that we do not have them in the UK, and the importance of the work for the UK and UK economy and public health was explained. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.diamond.ac.uk/Public/VisitUs.html |
| Description | Surrey Open day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | Described the research activity of the Pirbright Institute for students from school, graduate and postgraduate students, and provided information on research facilities in the institute. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.surrey.ac.uk/opendays/vet |