The two key factors for the generation of the diverse antigen receptor repertoire in the human adaptive immune system are the products of the recombination activating genes 1 and 2 (RAG1 and RAG2). The identification of their homologs, spRAG1L and spRAG2L respectively, in the genome of the purple sea urchin, Strongylocentrotus purpuratus was unexpected as there is no evidence thus far of an adaptive immune system in invertebrates (including echinoderms), i.e. they lack at least one of its hallmarks, a diversified antigen receptor repertoire. During this fiscal year we performed extensive mapping studies to identify the interaction surface between SpRag1L and SpRag2L. The interaction surface, at least in part, is homologous to that between mouse Rag1 and Rag2 suggesting an evolutionary conserved structure of the Rag1/Rag2 complex. In addition we generated hybrid proteins in which the DNA-binding domains of Rag1 and SpRag1L have been swapped. These proteins will be critical to determine the conservation of recombinase activity, and to identify the DNA substrate of the SpRag1L/SpRag2L complex. Our studies have major implications for the current model of how adaptive immunity evolved in jawed vertebrates, and will help to illuminate conserved features of how V(D)J recombination is tightly controlled to avoid potentially dangerous modifications of the genome.
| Fugmann, Sebastian D (2011) RAG-2 unleashed: lymphocytes beware. Immunity 34:137-9 |
| Litman, Gary W; Rast, Jonathan P; Fugmann, Sebastian D (2010) The origins of vertebrate adaptive immunity. Nat Rev Immunol 10:543-53 |
| Fugmann, Sebastian D (2010) The origins of the Rag genes--from transposition to V(D)J recombination. Semin Immunol 22:10-6 |
