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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1747-1754.
Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-08-2828.

Submitted August 18, 2003
Accepted October 22, 2003
Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant
Tao Wan, Xiangyang Zhou, Guoyou Chen, Huazhang An, Taoyong Chen, Weiping Zhang, Shuxun Liu, Yingming Jiang, Feng Yang, Yanfeng Wu, and Xuetao Cao*
Institute of Immunology, Second Military Medical Universty, Shanghai, China
* Corresponding author; email: caoxt{at}public3.sta.net.cn.
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 (DC) has potent adjuvant effects that polarize responses towards Th1. With a calculated molecular weight of 54.8 kD, Hsp70L1 is smaller in size than Hsp70, but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DC with Hsp70 and can interact with DC, promoting DC maturation, and stimulating secretion of the proinflammatory cytokines IL-12p70, IL-1 and TNF- and the chemokines IP-10 , MIP-1 , MIP-1 and RANTES. The induction of 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-OVA257-264 induces an OVA257-264-specific Th1 response and CTL that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DC 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.

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