Hsu 9723203 Technical Section The flexibility and adaptivity of the vertebrate immune system to the environment is based on the extraordinarily wide diversity of the cell surface receptors that mediate immune function. In vertebrates, large multigene families and a unique mechanism of recombination brings together different gene segments that are expressed in lymphocytes. In the living representatives of the earliest vertebrates, the jawless fishes and in the jawed cartilaginous fishes, it is not clear if expression is dependent on gene rearrangement in the latter or if a multigene family exists in the former. The specific aims of this work are: to isolate VH-like sequences from jawless fish by the new PCR approach developed in this laboratory in order to identify a multigene family encoding lymphocyte cell receptors in representatives of the most primitive vertebrates, to compare the expression of the shark joined and unjoined IG genes in order to determine the role of the recombination process in Ig expression in jawed vertebrates, and to investigate the regulation of IG expression in sharks with respect to allelic/isotype exclusion, in order to determine if the lymphocytes are polyspecific. Non-technical section The proposed experiments will expand our insight into the existence and role of multigene families and the rearrangement process in the representatives of the earliest vertebrates and allow a better understanding of how the modern, adaptive immune system evolved specific, clonal recognition of pathogenic non-self. ***
