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Serpinb9 (Spi6)‐deficient mice are impaired in dendritic cell‐mediated antigen cross‐presentation
Author(s) -
Rizzitelli Alexandra,
Meuter Simone,
Vega Ramos Javier,
Bird Catherina H,
Mintern Justine D,
Mangan Matthew SJ,
Villadangos Jose,
Bird Phillip I
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2012.29
Subject(s) - cytotoxic t cell , cross presentation , priming (agriculture) , antigen presentation , antigen , antigen processing , mhc class i , cd8 , major histocompatibility complex , immunology , dendritic cell , t cell , biology , granzyme b , antigen presenting cell , microbiology and biotechnology , immune system , genetics , in vitro , germination , botany
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.