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Abstract The water buffalo is considered an essential component of the Egyptian animal wealth. They produce about 60% of totally produced milk and about 40% of the totally produced meat in Egypt. So, water buffalo becomes central to the Egyptian farm animals and the Egyptian government tries hard on controlling the infectious agents among such species by the application of control programs based primarily on immunological aspects. One of the major difficulties for the application of such control programs was the slow progress in elucidating the mechanisms regulating the immune response to the infectious agents and their derived vaccines. This was the result of lack of mAbs reagents needed for studying the immune system and immune response in water buffalo. So, the aim of the present study was to provide an insight toward the immune system of water buffalo using mAbs and flow cytometry technology. This was achieved by; 1- Screening of a large set of mAbs that recognize bovine MHC and leukocyte differentiation molecules to identify mAbs that react with orthologous molecules in water buffalo. It was found that analysis of ninety mAbs developed against leukocyte differentiation molecules in cattle, sheep, goats, lama, pigs, dogs and human revealed that these mAbs recognize conserved epitopes on orthologous leukocyte differentiation molecules in water buffalo. This includes mAbs specific for MHC class I, MHC class II, CD2, CD3, CD4, CD6, CD8, CD11a, CD11b, CD11c, CD14, CD18, CD25, CD44, CD45R, CD62L, CD172a. Also mAbs that recognize γδ TCR, WC1 molecules expressed on activated lymphocytes were identified |