Journal article
Systems-guided forward genetic screen reveals a critical role of the replication stress response protein ETAA1 in T cell clonal expansion
LA Miosge, Y Sontani, A Chuah, K Horikawa, TA Russell, Y Meia, MV Wagle, DR Howard, A Enders, DC Tscharke, CC Goodnow, IA Parish
Proceedings of the National Academy of Sciences of the United States of America | Published : 2017
Abstract
T-cell immunity requires extremely rapid clonal proliferation of rare, antigen-specific T lymphocytes to form effector cells. Here we identify a critical role for ETAA1 in this process by surveying random germ line mutations in mice using exome sequencing and bioinformatic annotation to prioritize mutations in genes of unknown function with potential effects on the immune system, followed by breeding to homozygosity and testing for immune system phenotypes. Effector CD8+ and CD4+ T-cell formation following immunization, lymphocytic choriomeningitis virus (LCMV) infection, or herpes simplex virus 1 (HSV1) infection was profoundly decreased despite normal immune cell development in adultmice h..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank the National Computational Infrastructure (Australia) for continued access to significant computation resources and technical expertise; the staff of the Australian Phenomics Facility for animal husbandry, DNA preparation, and genotyping; the staff of Australian Cancer Research Foundation Biomolecular Resource Facility for exome and Sanger sequencing; and the staff of the Microscopy and Cytometry Resource Facility for help with flow cytometry. This work was funded by National Institutes of Health Grant U19-AI100627; by the National Health and Medical Research Council through Program Grants 1016953 and 1113904, Australia Fellowship 585490, Senior Principal Research Fellowship 1081858, and C.J. Martin Early Career Fellowship 585518 (to I.A.P.); and by the National Collaborative Research Infrastructure Strategy.