Isolation and Identification of Renal Cell Carcinoma-Derived Peptides Associated with GP96

Abstract

We determined the possible associated determinants and analyzed whether gp96-associated antigenic peptides can be found in renal cell carcinoma (RCC). The gp96-peptide complexes were chromatographically purified from resected tumor tissue of RCC patients. SDS-PAGE and Western blot analysis confirmed gp96 using the gp96 monoclonal antibody, and its con- are small molecular peptides, and the two peptides are deduced to be RCC-associated peptides. The identified peptides were confirmed to be associated with gp96 using the protocols described above. However, the specificity and relevance of the association to the immunogenicity of gp96 remains to be examined. Further analysis must be accomplished before the findings can be applied in peptide vaccine.

HSPs drive dichotomous T-cell immune responses via DNA methylome remodelling in antigen presenting cells

“…We have previously shown that immunization with low-dose gp96 leads to priming of anti-tumour immune responses1210111230. This is in stark contrast to responses primed by high-dose gp96 shown here.…”

“…The prototypical immunogenic HSP, gp96, is a ubiquitous intracellular chaperone that binds to a variety of endogenous peptides12. After release from damaged cells in situ or through administration via vaccination, gp96 engages its receptor CD91 expressed on the surface of antigen-presenting cells (APCs)3456789.…”

Functions of Heat Shock Proteins in Pathways of the Innate and Adaptive Immune System

“…When peptides are eluted from highly purified, apparently homogenous HSPs, MHC binding peptides and their precursors (intermediates of the processing events) are found 8–10,12–29 ,…”

“…Peptide binding sites have been identified for calreticulin 5 and hsp90 6 and its ER paralogue gp96 7 . For each of these HSP, peptides associate to HSPs with low affinity and no or low specificity 8–10 . The peptides are generally 10–30 amino acids in length and are generated during normal protein turnover in cells 8–10 .…”

“…For each of these HSP, peptides associate to HSPs with low affinity and no or low specificity 8–10 . The peptides are generally 10–30 amino acids in length and are generated during normal protein turnover in cells 8–10 . Since peptide binding sites for each HSP are different, the case can be made for distinct associated peptide repertoires.…”