Infectious disease studies in tuberculosis and papillomavirus have shown humans and rabbits share similar pathology and rabbits are more phylogenetically similar to primates than rodents. The use of the rabbit model is hindered by the lack of species-specific immunological reagents. In this proposal, we will take a rational approach to generate the most critical reagents that are essential for sorting and in vitro culture of subsets of immune cells (B, T and NK cells, monocytes and granulocytes) to adaptively boost the development of a practical panel of reagents for comprehensive profiling of the rabbit cell-mediated immunity. The proposal will discover antibodies to detect cell surface markers on rabbit B and T cells. Negative selection of the dominant B and T cell populations will better resolve other immune cells types (NK cells) and provides opportunity to find new cell surface markers to develop antibodies against. The proposed work will evaluate discovery of single variable domain antibodies to serve as versatile reagents in a comprehensive immunophenotyping panel that can be formatted for flow cytometry, immunostaining, and cell isolation.