The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9

Koichi Tabeta, Kasper Hoebe, Edith M. Janssen, Xin Du, Philippe Georgel, Karine Crozat, Suzanne Mudd, Navjiwan Mann, Sosathya Sovath, Jason Goode, Louis Shamel, Anat A. Herskovits, Daniel A. Portnoy, Michael Cooke, Lisa M. Tarantino, Tim Wiltshire, Benjamin E. Steinberg, Sergio Grinstein, Bruce Beutler

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Abstract

Here we have identified 'triple D' (3d), a recessive N-ethyl-N-nitrosourea-induced mutation and phenotype in which no signaling occurs via the intracellular Toll-like receptors 3, 7 and 9 (sensors for double-stranded RNA, single-stranded RNA and unmethylated DNA, respectively). The 3d mutation also prevented cross-presentation and diminished major histocompatibility complex class II presentation of exogenous antigen; it also caused hypersusceptibility to infection by mouse cytomegalovirus and other microbes. By positional identification, we found 3d to be a missense allele of Unc93b1, which encodes the 12-membrane-spanning protein UNC-93B, a highly conserved molecule found in the endoplasmic reticulum with multiple paralogs in mammals. Innate responses to nucleic acids and exogenous antigen presentation, which both initiate in endosomes, thus seem to depend on an endoplasmic reticulum-resident protein, which suggests communication between these organellar systems.

Original languageEnglish (US)
Pages (from-to)156-164
Number of pages9
JournalNature immunology
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2006

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Tabeta, K., Hoebe, K., Janssen, E. M., Du, X., Georgel, P., Crozat, K., Mudd, S., Mann, N., Sovath, S., Goode, J., Shamel, L., Herskovits, A. A., Portnoy, D. A., Cooke, M., Tarantino, L. M., Wiltshire, T., Steinberg, B. E., Grinstein, S., & Beutler, B. (2006). The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nature immunology, 7(2), 156-164. https://doi.org/10.1038/ni1297