Roles of MHC class Ia and class Ib in hsp70 mediated anti-tumor responses in the frog Xenopus (43.11)

Abstract The heat shock proteins (hsps) gp96 and hsp70 mediate potent antigen-dependent anti-tumor responses in both mammals and Xenopus. We have developed an adoptive cell transfer assay using peritoneal leukocytes as antigen presenting cells (APCs), and shown that hsp72, but not hsc73, is as potent as gp96 to prime T cell responses in vivo against the Xenopus thymic tumor 15/0 that is tumorigenic when transplanted in MHC-compatible Xenopus clones. The 15/0 tumor expresses several nonclassical MHC class Ib genes and β2-m, however it does not express classical MHC class Ia. Despite the lack of class Ia expression by 15/0, Xenopus adults generate potent cytotoxic CD8 T cell effectors (CCU-CTLs) that specifically recognize and kill the 15/0 tumor. We postulate that hsp72, but not hsc73, can prime class Ib-mediated anti-tumor CCU-CTL responses by interacting with APCs. To reveal the roles of class Ia and class Ib in this process we silenced surface expression of both molecules on APCs and assessed the effects in priming hsp72- or hsc73-mediated tumor immunity by adoptive transfer. To further elucidate the involvement of class Ia and class Ib in hsp70-mediated T cell function in vivo, we developed reliable transgenic techniques for our Xenopus clones and obtained F0 animals with silenced β2-m expression in vivo. This study allows us to gain better perspective into the intricate relationship between the two hsps, class Ia and class Ib molecules in T cell function as well as tumor immunity.