Tumor-specific immunogenicity of stress-induced proteins: convergence of two evolutionary pathways of antigen presentation?

Stress-induced proteins (hsps) elicit tumor-specific immunity to a number of murine tumors. Specificity of this immunity is puzzling in view of the fact that no tumor-specific DNA sequence polymorphisms have been identified in stress-induced genes, nor is there evidence for tumor-specific posttranslational modification of hsps. In this light, the possibility that hsps may not be antigenic per se, but may be carriers of antigenic moieties such as peptides, and may be accessory antigen-presenting molecules, is considered. A model where an hsp molecule such as gp96 acts as an intermediate in presentation of peptides to MHC is discussed and it is suggested that the hsp and MHC antigens are mediators of independent but functionally convergent phylogenetic pathways.