An Ancestral Immune Surveillance System in the Amphibian Xenopus Connecting Certain Heat Shock Proteins with Classical and Nonclassical MHC Class I Molecules

Abstract

Studies in the amphibian Xenopus, a vertebrate species that diverged from a common ancestor with mouse and human more than 350 million years ago, provide evolutionary insights into the convergent roles of certain hsps such as gp96 and HSP70 as well as classical and nonclassical MHC class I molecules in cancer immune surveillance. Evidence that in Xenopus gp96 and HSP70 can elicit potent antitumor responses dependent on antigen representation by nonclassical MHC class Ib molecules and presumably involving innate T cells suggests the existence of an ancestral immune surveillance system in antigen-presenting cells such as macrophages integrating hsps with classical and nonclassical MHC molecules. The particular connection revealed in Xenopus between hsps and nonclassical MHC molecules presenting conserved patterns to innate T cells affords new avenues to develop therapeutic strategies against cancer.