Cellular protein is the source of cross-priming antigen<i>in vivo</i>

Shen, Lianjun; Rock, Kenneth L.

doi:10.1073/pnas.0308345101

Cited by 176 publications

(149 citation statements)

References 40 publications

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“…Cross-priming is a crucial pathway of exogenous antigen presentation on the HLA class I molecules by APCs, enabling antiviral or antitumour responses (den Haan et al 2000;Sigal et al 1999). It has been shown that intact proteins or non-chaperoned proteasome products can be a source of antigens used for cross-presentation (Norbury et al 2004;Serna et al 2003;Shen and Rock 2004). However, these molecules were shown not to be as effective in cross-priming as peptides chaperoned by HSPs (Binder et al 2001;Binder and Srivastava 2005).…”

Section: Introductionmentioning

confidence: 99%

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Stocki

Morris

Preisinger

et al. 2010

Cell Stress and Chaperones

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Heat shock protein 70 (HSPA) is a molecular chaperone which has been suggested to shuttle human leukocyte antigen (HLA) epitope precursors from the proteasome to the transporter associated with antigen processing. Despite the reported observations that peptides chaperoned by HSPA are an effective source of antigens for cross-priming, little is known about the peptides involved in the process. In this study, we investigated the possible involvement of HSPA in HLA class I or class II antigen presentation and analysed the antigenic potential of the associated peptides. HSPA was purified from CCRF-CEM and K562 cell lines, and using mass spectrometry techniques, we identified 44 different peptides which were copurified with HSPA. The affinity of the identified peptides to two HSPA isoforms, HSPA1A and HSPA8, was confirmed using a peptide array. Four of the HSPAassociated peptides were matched with 13 previously reported HLA epitopes. Of these 13 peptides, nine were HLA class I and four were HLA class II epitopes. These results demonstrate the association of HSPA with HLA class I and class II epitopes, therefore providing further evidence for the involvement of HSPA in the antigen presentation process.

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Section: Introductionmentioning

confidence: 99%

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Stocki

Morris

Preisinger

et al. 2010

Cell Stress and Chaperones

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“…180 In addition, it has been shown that intact proteins, rather than exogenous or endogenous peptides or heat shock protein/peptide complexes, represent the major source of cross-priming antigens that are transferred from APCs. 181 Clinical trials using irradiated autologous wholetumour PC vaccines were initiated following demonstrating their efficiency in preclinical animal models of PC. 182 Autologous PC vaccines were initially used for treating eight PC patients in a phase I clinical trial.…”

Section: Whole-tumour Cell Vaccinesmentioning

confidence: 99%

Immunology and immunotherapy approaches for prostate cancer

Elkord

2007

Prostate Cancer Prostatic Dis

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Several mechanisms that impair the immune response to promote tumour progression are reported. These mechanisms aim to reduce the ability of antigen-presenting cells to present antigen and activate naïve T cells to support an active immune response or to create a suppressive environment that induce non-functional tumour-associated antigen-specific T cells. Prostate cancer (PC) alone accounts for 33% of incident cancer cases and about 9% of all cancer-related deaths among men in the USA during 2006. Whereas androgen deprivation has remained the first line of therapy for advanced PC, other therapies are still required due to progression to an androgen-resistant state and eventually loss of control in patients receiving hormonal therapy. Immunotherapy seems to be a promising approach to enhance tumour-specific T-cell responses in different cancers including prostate. More importantly, clinical trials in advanced PC patients have shown that immunotherapy may generate significant clinical responses. Immunology and immunotherapy aspects of PC with focus on prostate-specific antigen will be presented.

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“…[6], are involved in antigen cross-presentation and the consequent antiviral and anticancer immune response. Although the extent of chaperone-mediated antigenic peptides in cross-presentation has been debated [7,8], the necessity and sufficiency of peptides chaperoned by Hsps for antigen cross-priming of CD8 C T cells was recently shown [9,10]. However, the involvement of chaperones in cross-priming might also occur at the proteasomal substrate level [11] or by (chaperoneassisted) autophagy inducing MHC class II presentation of intracellular antigens [12].…”

Section: Glossarymentioning

confidence: 99%