Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant.
Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1. With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed and secreted (RANTES). The induction of interferon-gamma-inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1-ovalbumin(OVA)(257-264) induces an OVA(257-264)-specific Th1 response and cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases.
Wan
Tao
T
Institute of Immunology, Second Military Medical University, Shanghai, PR China.
Zhou
Xiangyang
X
Chen
Guoyou
G
An
Huazhang
H
Chen
Taoyong
T
Zhang
Weiping
W
Liu
Shuxun
S
Jiang
Yingming
Y
Yang
Feng
F
Wu
Yanfeng
Y
Cao
Xuetao
X
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D019496:Cancer Vaccines; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002469:Cell Separation; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D015723:Gene Library; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D011485:Protein Binding; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; C515370:CCR7 protein, human; D019496:Cancer Vaccines; C515371:Ccr7 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D018076:DNA, Complementary; D018840:HSP70 Heat-Shock Proteins; C483693:Hspa14 protein, human; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D010455:Peptides; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin; D008156:Luciferases