Cutting edge: Tumor secreted heat shock-fusion protein elicits CD8 cells for rejection

The endoplasmic reticulum resident heat shock protein gp96 chaperons peptid es, including those derived from tumor Ags, on their way to presentation by MHC class I. Replacement of the endoplasmic reticulum retention signal of gp96 with the Fe portion of murine IgG1 generated a secretory form of gp96, gp96-Ig. Tumor cells secreting gp96-Ig exhibited decreased tumorigenicity and increased immunogenicity in vivo and were rejected after initial growth . Rejection required CD8 T cells during the priming and effector phase, CD4 T cells were not required for rejection in either phase. Carrageenan, a co mpound known to inactivate macrophages in vivo, did not diminish CD8-mediat ed tumor rejection. Therefore, immunization with tumors secreting gp96-Ig g enerates efficient tumor-rejecting CD8 CTL without requirement for CD4 or m acrophage help. In contrast, immunization with purified, tumor-derived gp96 . or with irradiated tumor cells requires both.