A proposed mechanism for the induction of cytotoxic T lymphocyte production by heat shock fusion proteins.
A 65 kDa mycobacterial heat shock protein (hsp65), fused to a polypeptide that contains an octapeptide (SIYRYYGL) agonist for a particular T cell receptor (2C TCR), stimulated C57BL/6 mice as well as CD4-deficient mice to produce CD8+ cytolytic T lymphocytes (CTL) to the fusion partner's octapeptide. This and other hsp65 fusion proteins but not native hsp65 itself stimulated dendritic cells in vitro and in vivo to upregulate the levels of MHC (class I and II) and costimulatory (B7.2) molecules. The results suggest a mechanism for the general finding that hsp fusion proteins, having fusion partners of widely differing lengths and sequences, elicit CD8 CTL to peptides from the fusion partners without requiring exogenous adjuvants or the participation of CD4+ T cells.
Cho
B K
BK
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Palliser
D
D
Guillen
E
E
Wisniewski
J
J
Young
R A
RA
Chen
J
J
Eisen
H N
HN
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D011993:Recombinant Fusion Proteins; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins