Heat shock proteins and the antitumor T cell response.
Heat shock proteins (HSP) have been shown to participate in the antitumor T cell response. First, HSP play a crucial role in the intracellular pathway for antigen processing where HSP can make complexes with a broad spectrum of cellular proteins and peptides through their chaperone functions. In this pathway, macrophages are required for processing the chaperoned peptides to make stable molecules with the major histocompatibility complex (MHC) class I molecules, even when HSP-peptide complexes are exogenously administered. Through this pathway, vaccination with HSP-peptide complexes is thus able to elicit the response of CD8+ T cells specific for the chaperoned peptides. These findings suggest an essential role of HSP in 'cross-priming' and their usefulness for antitumor vaccination with tumor peptides. Second, HSP have been suggested to be expressed on the cell surface by transformation and, in addition, to function as antigen-presenting molecules for double negative T cells. Third, HSP derived from tumor cells have reportedly been recognized by T cells with either T cell receptor (TCR)-alphabeta or TCR-gammadelta. These lines of evidence therefore indicate that HSP may be potentially promising target molecules for antitumor T cell immunotherapy.
Harada
M
M
Department of Virology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. harada@bioreg.kyushu-u.ac.jp
Kimura
G
G
Nomoto
K
K
D000818:Animals; D017951:Antigen Presentation; D019496:Cancer Vaccines; D003602:Cytotoxicity, Immunologic; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta