This proposal requests renewed support for studies combining molecular immunology, protein chemistry and recombinant DNA technology to ascertain the properties of immunoglobulins of primitive vertebrate species and to identify and characterize the genes specifying them with respect to rearranging elements (Variable, Diversity, Joining and Constant regions), the multiplicity of these elements, and their arrangement. Future studies will focus on: 1) completion of the characterization of the genes specifying light chains in the sandbar shark, Carcharhinus plumbeus; 2) characterization of the gene sequence and arrangement for sandbar shark heavy chains, and 3) characterization of cyclostome immunoglobulins and their genes. The immune response is a complex and precisely-regulated defense mechanism that is present in all vertebrates. Antibodies play a major role in the vertebrate immune response. The vast preponderance of biochemical and molecular genetic studies of antibodies have been carried out in man, mouse and rabbit, but very few comparable studies have been carried out on primitive vertebrates. The goal of this research is to provide new information on the rearranging elements of antibody genes in primitive vertebrate species, sandbar sharks and lampreys. This information will enhance our understanding of the origins of the genetic events underlying the fundamental recognition and defense mechanisms of the vertebrate immune system.
