Enhanced Generation of Cytotoxic T Lymphocytes by Heat Shock Protein 70 Fusion Proteins Harboring Both CD8+T Cell and CD4+T Cell Epitopes

2010 ◽  
Vol 7 (5) ◽  
pp. 1715-1723 ◽  
Author(s):  
Seiji Takemoto ◽  
Makiya Nishikawa ◽  
Xin Guan ◽  
Yuji Ohno ◽  
Tomoya Yata ◽  
...  
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
T Lymphocytes ◽  
Heat Shock Protein ◽  
Cytotoxic T Lymphocytes ◽  
Heat Shock Protein 70 ◽  
Fusion Proteins ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
T Cell Epitopes

scholarly journals In Vivo Cytotoxic T Lymphocyte Elicitation by Mycobacterial Heat Shock Protein 70 Fusion Proteins Maps to a Discrete Domain and Is Cd4+ T Cell Independent

2000 ◽  
Vol 191 (2) ◽  
pp. 403-408 ◽  
Author(s):  
Qian Huang ◽  
Joan F.L. Richmond ◽  
Kimiko Suzue ◽  
Herman N. Eisen ◽  
Richard A. Young
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
T Lymphocytes ◽  
Heat Shock Protein ◽  
Fusion Proteins ◽  
Cytotoxic T Lymphocyte ◽  
Protein Domain ◽  
Cd4 T Cell ◽  
Fusion Partner

To gain insights into the mechanisms by which soluble heat shock protein (hsp) fusions can elicit CD8+ cytotoxic T lymphocytes (CTLs) against the fusion partner, mycobacterial (Mycobacterium tuberculosis) hsp70 was dissected to ascertain whether a particular hsp domain is necessary, and knockout mice were used to determine whether the fusion protein's immunogenicity is dependent on CD4+ T lymphocytes. We found that the ability to elicit CD8+ CTLs depends on a discrete 200–amino acid protein domain, indicating that the fusion protein's immunogenicity for CD8+ T cells does not require coupled chaperone function or peptide binding. Further, we found that ovalbumin (OVA).hsp70 fusion protein elicited anti-OVA CD8+ CTLs about equally well in CD4 knockout and wild-type C57BL/6 mice, and also when the hsp70 was of murine (self) origin. The ability of hsp70 fusion proteins to elicit CD4-independent CTL responses suggests that hsp70 fusion proteins may be useful for immunological prophylaxis and therapy against disease in CD4+ T cell–deficient individuals.

scholarly journals Tumor-derived heat shock protein 70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity

2004 ◽  
Vol 95 (3) ◽  
pp. 248-253 ◽  
Author(s):  
Gosei Ueda ◽  
Yasuaki Tamura ◽  
Itaru Hirai ◽  
Kenjirou Kamiguchi ◽  
Shingo Ichimiya ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Heat Shock ◽  
T Lymphocytes ◽  
Heat Shock Protein ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Immunity ◽  
Heat Shock Protein 70

scholarly journals Identification of human T cell epitopes in the Mycobacterium leprae heat shock protein 70-kD antigen

2008 ◽  
Vol 94 (3) ◽  
pp. 500-506 ◽  
Author(s):  
E. ADAMS ◽  
W. J. BRITTON ◽  
A. MORGAN ◽  
A. L. GOODSALL ◽  
A. BASTEN
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Mycobacterium Leprae ◽  
T Cell Epitopes ◽  
Human T Cell

scholarly journals CD4+ T cell responses to epitopes of self-heat shock protein 70 in patients with juvenile dermatomyositis

2011 ◽  
Vol 70 (Suppl 2) ◽  
pp. A44-A45 ◽  
Author(s):  
E. Koffeman ◽  
E. Elst ◽  
F. van Wijk ◽  
B. Prakken ◽  
A. van Royen-Kerkhof
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Juvenile Dermatomyositis ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease

2017 ◽  
Vol 85 (8) ◽  
Author(s):  
Lucia Trotta ◽  
Kathleen Weigt ◽  
Katina Schinnerling ◽  
Anika Geelhaar-Karsch ◽  
Gerrit Oelkers ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
T Cell Responses ◽  
Tropheryma Whipplei ◽  
Content Type ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei, the proportions of activated effector CD4+ T cells, determined as CD40L+ IFN-γ+, were significantly lower in patients with CWD than in healthy controls; CD8+ T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei-specific degranulation, although CD69+ IFN-γ+ CD8+ T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei-derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei-derived proteins may contribute to the pathogenesis of CWD.

scholarly journals Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexandria C Wells ◽  
Keith A Daniels ◽  
Constance C Angelou ◽  
Eric Fagerberg ◽  
Amy S Burnside ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Cell Responses

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.

Heat shock protein T-cell epitopes as immunogenic carriers in subunit vaccines

Peptides 1994 ◽  
1995 ◽  
pp. 841-842 ◽  
Author(s):  
R. van der Zee ◽  
S. M. Anderton ◽  
C. A. F. Buskens ◽  
E. Alonso de Velasco ◽  
W. van Eden
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
T Cell Epitopes ◽  
Subunit Vaccines
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