HUMAN HOMOLOG OF MURINE TUMOR REJECTION ANTIGEN GP96 - 5'-REGULATORY AND CODING REGIONS AND RELATIONSHIP TO STRESS-INDUCED PROTEINS

Cell-surface glycoproteins of 96 kDa (gp96) have been implicated in immunogenicity of methylcholanthrene-induced mouse sarcomas in syngeneic hosts. In view of the potential immunogenicity of gp96-related molecules in human tumors, we have defined the 5'-regulatory and complete coding regions of a human gp96 transcript. The 5'-regulatory region contains an imperfect heat shock element apart from other regulatory sequences. The amino acid sequence of human gp96 is 96% homologous to its murine counterpart and genes for the two molecules show significant homology between untranslated regions. Comparison of gp96 sequences to other sequences in DNA and protein data bases indicates significant homology with the stress proteins 94-kDa glucose-regulated protein (grp94) and 108-kDa heat shock protein (hsp108) and 99-kDa endoplasmic reticular protein (ERp99). These molecules are either identical or represent a family of closely related molecules. With regard to their role in tumor immunity, it needs to be determined whether gp96 molecules are tumor antigens per se or whether they serve as carriers of other immunogenic moieties.