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Research Project: Functional Identification of CD8 T-cell Specific Determinants in ASFV Georgia 2007/1 Isolate

Location: Foreign Animal Disease Research

Project Number: 3022-32000-063-014-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Aug 1, 2019
End Date: Dec 31, 2023

Objective:
ARS, PIADC and Centre de Recerca en Sanitat Animal (CRESA) will work together, leveraging resources and capabilities towards the identification of African Swine Fever Virus (ASFV) T-cell functional epitopes. This is a basic research project that will provide information to better understand the protective immune response to ASFV.

Approach:
Prediction of the location of T-cell epitopes using computer algorithms has been shown to be inaccurate, leading to a high frequency of failures when identified epitope are tested in experimental systems. Therefore, it is proposed here to use a direct identification of virus peptides present in the context of SLA-I antigens in the surface of antigen presenting cells. ASFV-specific CD8+ T-cell epitopes will be identified using an immunopeptidomic approach based on the analysis of SLA I-bound peptides found in porcine alveolar macrophages (PAM) in vitro infected with ASFV. Preliminary studies at IRTA identified that BA71 delta CD2, a recombinant virus lacking the CD2v ORF, presents ASFV-specific SLAI-restricted peptides significantly better than the parental BA71 virus. Therefore, presence of CD2 appears to inhibit the spectrum of antigenic presentation mediated by SLA-I. The present proposal intends to extend these studies to Georgia2007/1 ASFV (Genotype II), the isolate currently circulating in Continental Europe and Asia. CReSA will provide expertise in the identification of SLA-I linked virus peptides in ASFV infected swine macrophages. Using an immunopeptidomic approach CReSA scientist will isolate and identify virus peptides processed and presented in the context of SLA-I swine macrophages. ARS, PIADC will provide CReSA scientist with ASFV strains lacking CD2-like virus genes in order to perform the immunopeptidomic methodology.