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Messmer, Michelle (2013) ANALYSIS OF CELLULAR SENTINELS FOR EXTRACELLULAR HEAT SHOCK PROTEIN-PEPTIDE COMPLEXES. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Since the discovery of gp96 in the 1980’s as a “tumor rejection antigen,” Heat Shock Proteins (HSPs) have received attention from immunologists for their ability to prime immune responses. Originally known for their important intracellular roles as chaperones to newly synthesized, misfolded, and/or recently degraded proteins, it is now understood that HSPs released into the extracellular environment can also initiate immune responses. Shown both in vitro and in vivo, HSPs act on antigen presenting cells (APC) to 1) deliver antigenic peptides for presentation by both MHC class I and class II molecules and 2) activate APC to increase expression of co-stimulatory molecules. Both of these activities contribute to productive T cell responses, which has led to current trials using HSP-peptide complexes as cancer vaccines. However, the cell populations responsible for monitoring exogenous HSPs and priming resulting immune responses have yet to be fully characterized. This study identifies the cells that incorporate HSPs in vivo, following either vaccination or release by tumors, and analyzes the immune response generated by these cells. A CD11c+CD11b+CD4+ dendritic cell population selectively takes up HSPs, coincident with higher expression of the HSP receptor CD91 on these cells. We also show the dependence on CD91 of HSP-mediated immune responses. Increased knowledge of the process by which HSPs shape immune responses will contribute to the understanding of HSP-mediated immunity as well as assist in optimizing current tumor-vaccine strategies.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Messmer, Michellemim59@pitt.eduMIM59
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorBinder, Robertrjb42@pitt.eduRJB42
Committee MemberStorkus, Walterstorkuswj@upmc.eduSTORKUSW
Committee MemberMorelli, Adrian Emorelli@imap.pitt.eduMORELLI
Committee MemberSt. Croix, Claudettecls13@pitt.eduCLS13
Committee MemberKirkwood, JohnKirkwoodJM@upmc.eduKIRKWOOD
Committee MemberLiu,
Date: 4 December 2013
Date Type: Publication
Defense Date: 1 November 2013
Approval Date: 4 December 2013
Submission Date: 4 December 2013
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 119
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Immunology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Heat Shock Protein, cancer, vaccine, anti-tumor response, antigen presenting cell, CD91
Date Deposited: 04 Dec 2013 16:38
Last Modified: 19 Dec 2016 14:41


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