2006 Fiscal Year Final Research Report Summary
Identification of Hsp90-specific receptor expressed on human dendritic cells and its application for cancer immunothearpy
| Project/Area Number |
17590309
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
TAMURA Yasuaki Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (80322329)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Noriyuki Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (50158937)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Hsp90 / dendritic cell / cross-presentation / receptor / endocytosis |
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| Research Abstract |
It is well established that heat shock proteins (HSPs)-peptides complexes elicit antitumor responses in prophylactic and therapeutic immunization protocols. We have shown that Hsp90-antigen complexes undergo receptor-mediated uptake by antigen presenting cells (APCs) with subsequent representation of the HSP-associated peptides to MHC class I molecules on APCs, facilitating efficient cross-presentation. However, Hsp90 receptors expressed on APCs have not been identified yet. In particular, receptors for endocytosis of Hsp90-antigen complexes remain unknown. In this study, we have identified the candidate molecule for Hsp90 receptor using a expression cloning. Although this molecule is known as an ER-resident protein, we have confirmed the cell surface expression on human dendriric cells (DC). In addition, we demonstrated that this ER-resident protein interacted with exogenous Hsp90. Thus, this molecule has a unique character compared with other known HSP receptors, such as scavenger receptor A (SR-A), LOX-1 and CD91. We are examining that whether this molecule is involved in Hsp90-mediated cross-presentation by DCs. Furthermore, we are now making an effort to establish a mAb against this molecules for the antigen targeting to DCs for the cancer immunotherapy.
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