Efficient cross-priming of antiviral CD8+ T cells by antigen donor cells is GRP94 independent.
Cross-priming, the activation of naive CD8+ T cells by dendritic cells presenting Ags synthesized by other cells, is believed to play an important role in the generation of antiviral and antitumor responses. The molecular mechanism(s) underlying cross-priming remain poorly defined and highly controversial. GRP94 (gp96), an abundant endoplasmic reticulum chaperone with innate immune-activating capacity, has been widely reported to play a major role in cross-priming. In this study, we show that cells whose expression of GRP94 is silenced via transient or stable transfection with GRP94-directed small interfering RNAs demonstrate no reduction in their abilities to generate class I peptide complexes in cultured cells or to prime antiviral CD8+ T cell responses in vivo. In demonstrating the dispensability of GRP94, our finding points to the importance of alternative mechanisms for generation of class I peptide complexes from endogenous and exogenous Ags and immunogens.
Lev
Avital
A
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Dimberu
Peniel
P
Das
Suman R
SR
Maynard
Jason C
JC
Nicchitta
Christopher V
CV
Bennink
Jack R
JR
Yewdell
Jonathan W
JW
D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology*; D000998:Antiviral Agents / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology*; D002460:Cell Line; D045142:Cross-Priming / Q000276:immunology*; D005260:Female; D055785:Gene Knockdown Techniques; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D000998:Antiviral Agents; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C053387:endoplasmin