第35回 進化多様性生物学セミナー

日時：9月19日（火）14：00-15：00

場所：理学部２号館　223号室

演者

　Dr. Jacques Robert (University of Rochester Medical Center)

演題

EVOLUTION OF STRESS PROTEINS AS SPECIALIZED AGENTS OF IMMUNE SURVEILLANCE AND ANTI-TUMOR IMMUNITY

要旨

　The unique immunological activities of stress or heat shock proteins (hsps) such as hsp70 and gp96 appears to rely on two main properties: (1) a peptide-dependent capacity to chaperone and elicit adaptive CTL responses against antigenic peptides, and a (2) a peptide-independent capacity to stimulate pro-inflammatory innate immune responses. The relationship and relative biological relevance of these properties are unclear. To evaluate the importance of hsps in immune response, we have developed a comparative tumor-immunity model in the frog Xenopus, a species whose evolutionary distance from mammals permits distinguishing species-specific adaptation or specialization from more fundamental and conserved features. This model includes: MHC identical but minor histocompatibility (H) antigen-disparate cloned frogs; MHC class Ia-negative tumors transplantable in these different Xenopus clones; and a larval immune system that is naturally class I-deficient.

We have shown that like mammalian hsps, Xenopus hsp70 and gp96 generates antigen-specific,　MHC-restricted CD8 T cell response involving cross-presentation. In addition, gp96, at least in Xenopus, is also able to elicit potent and specific immunity against a tumor that does not express class I molecules. Further characterization by in vitro killing assays, RNA interference and adoptive cell transfers reveals that whereas gp96 generates typical class Ia-restricted CTL against chaperoned minor H-antigens, it generates, against tumors, potent NK cells and CTLs that interact with non-classical class Ib molecules.

Overall our studies suggest that the interaction of hsps with the immune system is evolutionarily ancient and has diversified to stimulate a complex network of effectors.

世話人：免疫分子進化学研究室　野中　勝　（内線27589）