Serpinb9 (Spi6)-deficient mice are impaired in dendritic cell-mediated antigen cross-presentation

Immunol Cell Biol. 2012 Oct;90(9):841-51. doi: 10.1038/icb.2012.29. Epub 2012 Jul 17.

Abstract

Serpinb9 (Sb9, also called Spi6) is an intracellular inhibitor of granzyme B (GrB) that protects activated cytotoxic lymphocytes from apoptosis. We show here that the CD8(+) subset of splenic dendritic cells (DC), specialized in major histocompatibility complex class I (MHC I) presentation of exogenous antigens (cross-presentation), produce high levels of Sb9. Mice deficient in Sb9 are unable to generate a cytotoxic T-cell response against cell-associated antigen by cross-presentation, but maintain normal MHC-II presentation to helper T cells. This impaired cross-priming ability is autonomous to DC and is evident in animals deficient in both Sb9 and GrB, indicating that this role of Sb9 in DC is GrB-independent. In Sb9-deficient mice, CD8(+) DC develop normally, survive as well as wild-type DC after antigenic challenge, and exhibit unimpaired capacity to take up antigen. Although the core processing machinery is unaffected, Sb9-deficient DC appear to process antigen faster. Our results point to a novel, GrB-independent role for Sb9 in DC cross-priming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cells, Cultured
  • Cross-Priming / genetics
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Flow Cytometry
  • Granzymes / genetics
  • Granzymes / immunology
  • Granzymes / metabolism
  • H-2 Antigens / immunology
  • Immunoblotting
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / immunology*
  • Serine Endopeptidases / metabolism
  • Serpins / genetics
  • Serpins / immunology*
  • Serpins / metabolism
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • H-2 Antigens
  • Membrane Proteins
  • Serpins
  • Granzymes
  • Serine Endopeptidases
  • Serpinb9 protein, mouse