Immune self recognition in Drosophila: tuSz mutants exhibit an aberrant self-directed immune response. Nathan T. Mortimer, Todd A. Schlenke. Department of Biology, Emory University, Atlanta, GA.

   Drosophila melanogaster larvae are commonly infected by parasitoid wasps and mount a robust cellular immune response following parasitization. This immune response culminates in the melanotic encapsulation of the wasp egg, however, the molecular mechanisms by which fly immune cells recognize the wasp egg as foreign are unknown. Flies mount a similar encapsulation response against xenografts or abiotic objects, suggesting that rather than non-self recognition, the melanotic encapsulation response may be initiated by missing-self recognition. In this process, immune cells recognize a distinctive mark on self tissues, and the absence of this mark is sufficient to direct an immune response against a foreign object. The identity of the D. melanogaster self signal is unknown but mutations have been isolated in which larvae mount a self-directed cellular immune response, presumably due to the absence of, or the inability to recognize, such a signal. To gain insight into the mechanisms underlying this system, I have chosen to characterize one such mutant, tumor(1)Suzuki (tuSz), in which caudal fat body tissue is targeted for self-encapsulation. I found that the phenotype genetically maps to two closely linked loci. One mutation maps to hopscotch, the D. melanogaster JAK homolog, and causes ectopic activation of the cellular immune response. The mutation in the second locus disrupts protein N-glycosylation, and I found that both mutations are required for the self-encapsulation phenotype. These findings suggest that the D. melanogaster self mark is dependent on protein N-glycosylation, and that this mark is recognized by immune cells following activation of the cellular immune response.