CHARACTERIZATION IN-VITRO AND IN-VIVO OF THE PIG ANALOG OF HUMAN CD59USING NEW MONOCLONAL-ANTIBODIES

CD59 is the sole characterized regulator of the complement membrane at tack complex in humans. It is very widely and abundantly distributed, being present on all circulating cells, endothelia and epithelia, and in most tissues. CD59 analogues in rodents are distributed similarly. Interest in complement regulation in the pig has developed out of the current enthusiasm to exploit this species as a donor in xenotransplan tation of organs to humans. We have recently isolated and closed the p ig analogue of human CD59. We here report the development and characte rization of monoclonal antibodies against pig CD59, We have used these antibodies to develop efficient methods for the purification of pig C D59 to homogeneity from erythrocyte membranes and have obtained new in formation on the structure and function of the purified protein. The a ntibodies were found to function well in immunohistochemistry and have been used to perform a comprehensive survey of the expression and dis tribution of pig CD59 on cells and in organs of normal pigs. Pig CD59, like human CD59, is broadly expressed but there are some striking dif ferences in tissue distribution, notably the apparent lack of pig CD59 on circulating platelets and on a subset of leucocytes in blood and l ymphoid organs. The reported findings have important implications for the current approaches to avoiding complement-mediated hyperacute reje ction in pig-to-human xenografts.