Investigating highly specific innate immune responses in shrimp connected with the diversified IgSF molecule, Dscam KC Han-Ching Wang Institute of Biotechnology, National Cheng Kung University, Tainan 701, Taiwan wanghc@mail.ncku.edu.tw Although adaptive immune systems and antibodies are not found in invertebrates, some arthropods have exhibited innate immune responses supplemented by a novel immune-system that exhibits both specificity and memory. The mechanisms underlying this unique immune system are still unclear. Some evidence suggests that the arthropod Dscam molecule (Down syndrome cell adhesion molecule) may potentially function as a specific receptor for pathogen recognition. Arthropod Dscams are generated through mutually exclusive alternative splicing, creating a striking hypervariability. This seems to be related to its antibody-like function in immune defense. These molecules consist of a hypervariable extracellular region which functions in pathogen recognition, and a cytoplasmic tail related to subsequent signal transduction. After isolating the first Dscams from shrimp (LvDscam and PmDscam isolated from Litopenaeus vannamei and Penaeus monodon), we found that these Dscams shared extracellular domain architecture typical of arthropod Dscams (9Ig-4FNIII-Ig-TM). In shrimp Dscams, variable alternatively spliced events were produced by mutually exclusive alternative splicing. These involved, variously, the N-terminal Ig2, N-terminal Ig3, the entire Ig7 or the transmembrane domain located in the extracellular region as well as exon inclusion/exclusion in the cytoplasmic tail. Given this variability, LvDscam can potentially encode over than 54,000 unique isoforms. We demonstrated LvDscam expression after shrimp were injected with white spot syndrome virus (WSSV) or Vibrio harveyi. After pathogenic challenge, a greater number of LvDScam isoforms was expressed. It appears that the Ig2 and Ig3 variable regions are the primary loci of host specific immune response against pathogens. Intriguingly, phylogenetic analysis places LvDscam isoforms into two clades. Those expressed after V. harveyi challenge are separate from isoforms expressed in unchallenged shrimp. Future research may reveal possible specific V. harveyi inhibition activity of these induced LvDscam isoforms. Keywords: shrimp、highly specific innate immune responses、Dscam、WSSV、Vibrio harveyi