Online citations, reference lists, and bibliographies.
← Back to Search

Heat Shock Fusion Proteins As Vehicles For Antigen Delivery Into The Major Histocompatibility Complex Class I Presentation Pathway.

K. Suzue, X. Zhou, H. Eisen, R. Young
Published 1997 · Medicine, Biology

Cite This
Download PDF
Analyze on Scholarcy
Mice immunized with heat shock proteins (hsps) isolated from mouse tumor cells (donor cells) produce CD8 cytotoxic T lymphocytes (CTL) that recognize donor cell peptides in association with the major histocompatibility complex (MHC) class I proteins of the responding mouse. The CTL are induced apparently because peptides noncovalently associated with the isolated hsp molecules can enter the MHC class I antigen processing pathway of professional antigen-presenting cells. Using a recombinant heat shock fusion protein with a large fragment of ovalbumin covalently linked to mycobacterial hsp70, we show here that when the soluble fusion protein was injected without adjuvant into H-2b mice, CTL were produced that recognized an ovalbumin-derived peptide, SIINFEKL, in association with Kb. The peptide is known to arise from natural processing of ovalbumin in H-2b mouse cells, and CTL from the ovalbumin-hsp70-immunized mice and a highly effective CTL clone (4G3) raised against ovalbumin-expressing EL4 tumor cells (EG7-OVA) were equally effective in terms of the concentration of SIINFEKL required for half-maximal lysis in a CTL assay. The mice were also protected against lethal challenge with ovalbumin-expressing melanoma tumor cells. Because large protein fragments or whole proteins serving as fusion partners can be cleaved into short peptides in the MHC class I processing pathway, hsp fusion proteins of the type described here are promising candidates for vaccines aimed at eliciting CD8 CTL in populations of MHC-disparate individuals.
This paper references
Post-translational protein translocation: not all hsc70s are created equal.
J. Brodsky (1996)
MHC class I-restricted CTL responses to exogenous antigens.
M. Jondal (1996)
Stress proteins are immune targets in leprosy and tuberculosis.
D. Young (1988)
T cell responses of normal individuals towards recombinant protein antigens of Mycobacterium tuberculosis
M. E. Munk (1988)
Sequence of chicken ovalbumin mRNA
L. McReynolds (1978)
Adjuvant-free hsp70 fusion protein system elicits humoral and cellular immune responses to HIV-1 p24.
K. Suzue (1996)
Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization
F. Carbone (1989)
A major immunogen in Schistosoma mansoni infections is homologous to the heat-shock protein Hsp70
R. Hedstrom (1987)
Introduction of soluble protein into the class I pathway of antigen processing and presentation
M. Moore (1988)
Peptide-binding specificity of the molecular chaperone BiP
G. Flynn (1991)
Tumor rejection antigen gp96/grp94 is an ATPase: implications for protein folding and antigen presentation.
Z. Li (1993)
Peptide binding and release by proteins implicated as catalysts of protein assembly.
G. Flynn (1989)
Cognate peptides induce self-destruction of CD8+ cytolytic T lymphocytes.
P. Walden (1990)
The translation machinery and 70 kd heat shock protein cooperate in protein synthesis
R. J. Nelson (1992)
Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones
J. Frydman (1994)
Cellular requirements for tumor-specific immunity elicited by heat shock proteins: tumor rejection antigen gp96 primes CD8+ T cells in vivo.
H. Udono (1994)
Enumeration of T cells reactive with Mycobacterium tuberculosis organisms and specific for the recombinant mycobacterial 64‐kDa protein
S. Kaufmann (1987)
Heat shock protein 70-associated peptides elicit specific cancer immunity
H. Udono (1993)
Screening of a recombinant mycobacterial DNA library with polyclonal antiserum and molecular weight analysis of expressed antigens.
D. Young (1987)
Structural Analysis of Substrate Binding by the Molecular Chaperone DnaK
X. Zhu (1996)
Antigen recognition by class I-restricted T lymphocytes.
A. Townsend (1989)
Priming to heat shock proteins in infants vaccinated against pertussis.
G. del Giudice (1993)
Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity
L. Falo (1995)
Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96
D. Arnold (1995)
Molecular chaperones in protein folding: the art of avoiding sticky situations.
F. Hartl (1994)
Substrate specificity of the DnaK chaperone determined by screening cellulose‐bound peptide libraries
S. Rüdiger (1997)
Protein folding in the cell
Mary-Jane H. Gething (1992)
Generation, translocation, and presentation of MHC class I-restricted peptides.
M. Heemels (1995)
Antigen Presentation Pathways to Class I and Class II MHC‐Restricted T Lymphocytes
T. Braciale (1987)
A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides.
R. Suto (1995)
Isolation of an endogenously processed immunodominant viral peptide from the class I H–2Kb molecule
G. M. V. Bleek (1990)
Use of T7 RNA polymerase to direct expression of cloned genes.
F. W. Studier (1990)
Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo.
J. Byrne (1984)
Exact prediction of a natural T cell epitope
O. Rötzschke (1991)
Heat shock cognate 70 is a prominent immunogen in Brugian filariasis.
M. Selkirk (1989)
Intracellular transport of class I MHC molecules in antigen processing mutant cell lines.
K. Anderson (1993)
Resistance of primary CD8+ cytotoxic T lymphocytes to lysis by cytotoxic granules from cloned T cell lines.
C. Nagler-Anderson (1988)
Influences of Transporter Associated with Antigen Processing (TAP) on the Repertoire of Peptides Associated with the Endoplasmic Reticulum–resident Stress Protein gp96
D. Arnold (1997)
Isolation of an immunodominant viral peptide that is endogenously bound to the stress protein GP96/GRP94.
T. J. Nieland (1996)
Suzue et al
T. J. Nieland (1997)
Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90, and hsp70.
H. Udono (1994)
Molecular chaperones in cellular protein folding
F. Hartl (1996)
Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly.
R. Beckmann (1990)

This paper is referenced by
HSPPC-96: a personalised cancer vaccine
M. Caudill (2001)
Therapeutic Vaccines for Human Papillomaviruses
L. Gissmann (2001)
Evaluation of antibody responses elicited by immunization of mice with a pneumococcal antigen genetically fused to murine HSP70 and murine interleukin-4.
Dennis O. Gor (2006)
A fusogenic peptide expressed on the surface of Salmonella enterica elicits CTL responses to a dengue virus epitope.
R. Luria-Pérez (2007)
Dendritic cells pulsed with gp96-peptide complexes derived from human hepatocellular carcinoma (HCC) induce specific cytotoxic T lymphocytes
X. Wang (2005)
Current ideas about applications of heat shock proteins in vaccine design and immunotherapy
X.-Y. Wang (2005)
Cross-Processing and -Presentation by B Fusion Protein Enhances Class I MHC Mycobacterium tuberculosis Heat Shock
Aaron A. R. Tobian (2013)
A proposed mechanism for the induction of cytotoxic T lymphocyte production by heat shock fusion proteins.
B. K. Cho (2000)
Prokaryotic Expression of Influenza A virus Nucleoprotein Fused to Mycobacterial Heat Shock Protein70
Zahra Yousefi-Najafabadi (2013)
12 Toxin in the development of vaccines
J. Hwang (2002)
Novel Vaccine Adjuvants
A. Agrawal (2013)
Murine Dendritic Cells Cross-Presentation of a Soluble Protein by Multiple Intracellular Routes in the Eisen
D. Palliser (2005)
Peripheral blood mononuclear cell proliferation to heat shock protein-70 derived from autologous lung carcinoma.
A. Michils (2002)
Therapeutic vaccination for the treatment of mucosotropic human papillomavirus-associated disease
N. Chu (2003)
Preventative and therapeutic vaccines for cervical cancer
R. Roden (2003)
Heat shock proteins as vaccine adjuvants
K. R. Qazi (2005)
Enhanced generation of cytotoxic T lymphocytes by increased cytosolic delivery of MHC class I epitope fused to mouse heat shock protein 70 via polyhistidine conjugation.
Seiji Takemoto (2009)
DNAvaccine encoding heat shock protein 60 co-linked to HPV 16 E 6 and E 7 tumor antigens generates more potent immunotherapeutic effects than respective E 6 or E 7 tumor antigens
Chia-Yen Huang (2007)
Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70.
H. Udono (2001)
Cancer Gene Therapy: Past Achievements and Future Challenges
N. Habib (2002)
Molecular Chaperone GroEL - toward a Nano Toolkit in Protein Engineering, Production and Pharmacy
A. N. Fedorov (2018)
Heat-shock proteins as activators of the innate immune system.
H. Bausinger (2002)
Enhanced immunogenicity of HPV16E7 accompanied by Gp96 as an adjuvant in two vaccination strategies.
A. Bolhassani (2008)
The potential of clusterin to act as an immune modulator
Rebecca A. Dabbs (2013)
Cancer immunotherapy: stress proteins and hyperthermia
M. Manjili (2002)
Molecular chaperones: biology and prospects for pharmacological intervention.
D. Smith (1998)
Heat Shock Protein-Based Therapeutic Strategies Against Human Immunodeficiency Virus
B. Brenner (1999)
Human CD8+ CTL Specific for the Mycobacterial Major Secreted Antigen 85A1
S. Smith (2000)
Purification of heat shock protein 70-associated tumor peptides and its antitumor immunity on hepatoma in mice
D. Chen (2004)
The N-terminal fragment of GRP94 is sufficient for peptide presentation via professional antigen-presenting cells.
C. Biswas (2006)
Immunization with the recombinant surface protein rTcSP2 alone or fused to the CHP or ATPase domain of TcHSP70 induces protection against acute Trypanosoma cruzi infection
Alej (2010)
Comparison of PSA-specific CD8+ CTL responses and antitumor immunity generated by plasmid DNA vaccines encoding PSA-HSP chimeric proteins
M. Pavlenko (2004)
See more
Semantic Scholar Logo Some data provided by SemanticScholar