HSP110 induces “danger signals” upon interaction with antigen presenting cells and mouse mammary carcinoma

Manjili, Masoud H.; Park, Jun-Eui; Facciponte, John G.; Subjeck, John R.

doi:10.1016/j.imbio.2005.04.002

Cited by 35 publications

(22 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our studies, we use autologous (mouse in mouse) grp170. However, we found that mouse hsp110 or grp170 could simulate cytokine release from mouse bone marrow-derived dendritic cells (46,47). Another important difference between the present study and other studies is that we examine grp170-protein interactions similar to previously described interactions exhibited by grp170, hsp70 and other stress proteins in situ (14,19,48), and not HSP-peptides.…”

Section: Discussionmentioning

confidence: 60%

Chaperoning Function of Stress Protein grp170, a Member of the hsp70 Superfamily, Is Responsible for its Immunoadjuvant Activity

et al. 2006

Self Cite

View full text Add to dashboard Cite

When used as vaccines, tumor-derived stress proteins can elicit antitumor immune responses. For members of the hsp70 superfamily, like grp170, this seems to be due to (a) the chaperoning of antigenic peptide by the stress protein and (b) the binding of the stress protein to receptor(s) on antigenpresenting cells (APC) and subsequent antigen presentation. This suggests that domains exist on the stress protein for each function. In this study, we determine the ability of grp170 and its structural domains to (a) bind to and present melanoma-associated antigen gp100 to the immune system and (b) to bind to receptors on APCs. A direct correlation between chaperone function, binding to APCs in a receptorlike manner, and antitumor immunity was observed. Two mutants that share no common sequence, yet are both effective in their antitumor activities, compete with one another for APC binding. Studies of other members of the hsp70 superfamily, hsp110 and hsp70, or their domain deletion mutants, further confirmed that APC binding segregates with chaperoning function and not sequence. Therefore, these studies suggest that molecular chaperoning is involved in stress protein interactions with APCs, antigen binding, and in eliciting antitumor immunity, thus bridging this ancient function of stress proteins in prokaryotes to their ability to elicit immunity in higher organisms. (Cancer Res 2006; 66(2): 1161-8)

show abstract

Section: Discussionmentioning

confidence: 60%

Chaperoning Function of Stress Protein grp170, a Member of the hsp70 Superfamily, Is Responsible for its Immunoadjuvant Activity

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, Hsp binding and stimulation through NKG2D/NKRP2 display a novel mode of action in contrast to that of distinct pattern recognition receptors. Higher Hsp110 has been shown to act as a "danger signal" to DCs (55), and Hsp105/Hsp110-pulsed BMDCs induce the regression of intestinal adenomas in vivo (56). Recently, it was reported that some member of the "Hsp70-superfamily" binds to scavenger receptors extracellularly (57).…”

Section: Discussionmentioning

confidence: 99%

The Ischemia-Responsive Protein 94 (Irp94) Activates Dendritic Cells through NK Cell Receptor Protein-2/NK Group 2 Member D (NKR-P2/NKG2D) Leading to Their Maturation

Srivastava

Varalakshmi

Khar

2008

The Journal of Immunology

View full text Add to dashboard Cite

Tumor recognition and killing, the uptake of released immunogenic substrate, and the generation of immunity are crucial aspects of dendritic cell (DC)-mediated antitumor immune response. In the context of direct tumoricidal activity, we have recently shown NK cell receptor protein-2 (NKR-P2)/NK group 2 member D (NKG2D) as a potent activation receptor on rat DCs. The activation of DCs with agonistic anti-NKR-P2 mAb, the binding of soluble NKR-P2 to the AK-5 tumor, and DC maturation with fixed AK-5 cells led us to identify a putative NKR-P2 ligand on the AK-5 cell surface. In this study we have shown that the AK-5 tumor-derived ischemia-responsive protein-94 (Irp94, a 110 kDa Hsp family member) acts as a functional ligand for NKR-P2 on DCs and enhances Irp94-NKR-P2 interaction-dependent tumor cell apoptosis via NO. Surface expression of Irp94 was also found on tumors of diverse origin in addition to AK-5. Furthermore, the Th1-polarizing cytokine IL-12, produced from Irp94-ligated BMDCs, augments NK cell cytotoxicity. Irp94-NKR-P2 interaction drives the maturation of BMDCs by up-regulating MHC class II, CD86, and CD1a and also induces autologous T cell proliferation, which displays a crucial state of DCs for adaptive antitumor immune response. These functional properties of Irp94 reside in the COOH terminus subdomain but not in the NH2 terminus ATPase domain of Irp94. We also show the involvement of PI3K, ERK, protein kinase C, phosphatases, and NF-κB translocation as downstream mediators of DCs activation upon NKR-P2 ligation with Irp94. Our studies demonstrate for the first time a novel role of a 110-kDa heat shock protein (Irp94) as a ligand for NKR-P2 on DCs, which in turn executes both innate and adaptive immunity.

show abstract

“…DCs are known to ingest dying tumor cells and initiate tumor-specific responses when associated with appropriate danger signals, which are endogenous activation signals liberated by dying cells. Recent studies have shown that some intrinsic biochemical factors, such as uric acid, bradykinin and heat shock protein (HSP110) act as danger signals through their interaction with DCs, and influence the subsequent immune response (Aliberti et al, 2003;Shi et al, 2003;Manjili et al, 2005). Large amounts of uric acid can be produced following tissue injury in vivo, and activate the immune response against injured cells and dying tissues.…”

Section: Discussionmentioning

confidence: 99%

Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation

et al. 2007

View full text Add to dashboard Cite

Dendritic cells (DCs) are the most potent antigenpresenting cells and acquire cellular antigens and danger signals from dying cells to initiate antitumor immune responses via direct cell-to-cell interaction and cytokine production. The optimal forms of tumor cell death for priming DCs for the release of danger signals are not fully understood. OBP-301 (Telomelysin) is a telomerasespecific replication-competent adenovirus that induces selective E1 expression and exclusively kills human cancer cells. Here, we show that OBP-301 replication produced the endogenous danger signaling molecule, uric acid, in infected human tumor cells, which in turn stimulated DCs to produce interferon-c (IFN-c) and interleukin 12 (IL-12). Subsequently, IFN-c release upregulated the endogenous expression of the proteasome activator PA28 in tumor cells and resulted in the induction of cytotoxic T-lymphocytes. Our data suggest that virus-mediated oncolysis might be the effective stimulus for immature DCs to induce specific activity against human cancer cells.

show abstract

HSP110 induces “danger signals” upon interaction with antigen presenting cells and mouse mammary carcinoma

Cited by 35 publications

References 42 publications

Chaperoning Function of Stress Protein grp170, a Member of the hsp70 Superfamily, Is Responsible for its Immunoadjuvant Activity

Chaperoning Function of Stress Protein grp170, a Member of the hsp70 Superfamily, Is Responsible for its Immunoadjuvant Activity

The Ischemia-Responsive Protein 94 (Irp94) Activates Dendritic Cells through NK Cell Receptor Protein-2/NK Group 2 Member D (NKR-P2/NKG2D) Leading to Their Maturation

Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation

Contact Info

Product

Resources

About