Antigen Bias in T Cell Cross-Priming

Wolkers, Monika C.; Brouwenstijn, Nathalie; Bakker, Anke; Toebes, Mireille; Schumacher, Ton N.

doi:10.1126/science.1096268

Cited by 171 publications

(121 citation statements)

References 25 publications

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“…We used LyUV treatment of the ADC because it fully inactivated the virus and allowed for efficient NP396 crosspresentation similar to HEK-NP cells [7,8]. We initially expected that GP33 would fail to cross-present because it is located in the signal peptide of LCMV-GP [12], but it was cross-presented with low efficiency, probably due to its exceptional long half-life of 6 h [15]. Although NP396, located in the long-lived nucleoprotein [21], was efficient at cross-presentation, NP205 was poor, possibly due to inefficient processing by the phagosomal/proteasomal machineries.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, much of what is known about the cross-presentation of virus antigens is derived from studies relying on antigen donor cells (ADC) transfected with a single virus protein [7][8][9][10]. The ability of antigens to escape cytosolic degradation in ADC is important during cross-presentation [7,[11][12][13]. Interestingly, it appears that the capacity of an epitope to access cross-priming may support its immunodominance when considering the overall hierarchy [8,10,14].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, it appears that the capacity of an epitope to access cross-priming may support its immunodominance when considering the overall hierarchy [8,10,14]. Collectively, these findings seem to conflict with the immunodominant status of GP33 because this epitope is located in the signal sequence of the glycoprotein (lymphocytic choriomeningitis virus (LCMV)-GP) [15] and may not be able to cross-prime CTL [12].…”

Section: Introductionmentioning

confidence: 99%

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The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

et al. 2010

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The initiation of CD8 1 T cell (CTL) immune responses can occur via cross-priming. Recent data suggested a relationship between cross-presentation and immunodominance of epitope-specific T cells. To test this association, we evaluated the efficacy of crosspresentation for several virus epitopes in vitro and examined if this can be extrapolated in vivo. Employing lymphocytic choriomeningitis virus (LCMV), we demonstrate that the cross-presentation and cross-priming of LCMV antigens were dominated by NP396, but not NP205 when analyzing the LCMV-NP. Although with LCMV-GP, cross-presentation was dominated by GP276, and cross-priming was dominated by GP33. Importantly, although NP396 was significantly more efficient than GP33 in cross-presentation, cross-priming of their specific CTL was comparable. In a subsequent virus challenge after cross-priming, GP33-specific CTL dominated the response. Accordingly, based on our data, the ability of viral epitopes to be cross-presented in vitro does not entirely reflect what would occur in cross-priming. Thus, weak cross-presenting antigens may still cross-prime an efficient CTL response depending on other in vivo elements such as the naïve T-cell precursor frequencies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

et al. 2010

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“…First, the efficiency and specificity of priming will be increased due to the higher tumor antigen load in situ relative to that collected in the draining lymphoid tissues [16] and second, a broader repertoire of tumor-specific naïve T cells is recruited to the site of tumor antigens, leading to a more comprehensive response [35,41]. It has been shown that some tumor antigens may not be efficiently cross-presented due to the antigen bias in T cell cross-priming [42]. In these instances, we have demonstrated in our experimental system using the tumor cell line Ag104L d -LIGHT that certain antigens are presented to and activate naïve T cells within the tumor via a direct presentation mechanism [40,43].…”

Section: Light Creates Lymphoid-like Tissues Inside the Tumor To Imprmentioning

confidence: 99%

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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Metastastic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor superfamily member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells, NK cells, naïve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin β receptor (LTβR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy.

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“…59,70 It has been demonstrated that some tumor antigens may not be efficiently crosspresented due to the antigen bias in T-cell cross-priming. 71 Furthermore, no additional migration steps are required for CTLs to reach the site of effector function, which leads to the appearance of activated tumor-reactive T cells in a short period of time. In support of this reasoning, we demonstrated in our experimental system using the tumor cell line Ag104L d -LIGHT that certain antigens are presented to and activate naive T cells within the tumor via a direct presentation mechanism.…”

Section: Targeted Immunotherapy To Primary Tumor Tissues Can Generatementioning

confidence: 99%

Targeting and utilizing primary tumors as live vaccines: changing strategies

Yang

Mortenson

2011

Cell Mol Immunol

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Tumor metastases and relapse are the major causes of morbidity and mortality in cancer. Although surgery, chemotherapy and/or radiation therapy can typically control primary tumor growth, metastatic and relapsing tumors are often inaccessible or resistant to these treatments. An adaptive immune response can be generated during these conventional treatments of the primary tumor, and presumably both the primary tumor and secondary metastases share many of the same or similar antigenic characteristics recognized by the immune system. Thus, when established, this response should be able to control metastatic growth and tumor relapse. This review summarizes the mechanisms by which antitumor immune responses are generated, and recent findings supporting the hypothesis that many therapies targeting primary tumors can generate antitumor adaptive immune responses to prevent metastases and tumor relapse. Keywords: chemotherapy; immunotherapy; metastasis; radiotherapy; tumor vaccine INTRODUCTION Conventional treatments such as surgery and chemotherapy are effective means of eliminating or reducing primary tumor growth, but have not proved effective in eradicating metastases. Because metastatic disease may not respond similarly to chemotherapies used in treating the primary tumor, 1 recent research has focused on the importance of generating an antitumor immune response to control metastatic disease. Presumably, both the primary tumor and secondary metastases share many of the same or similar antigenic characteristics recognized by the immune system; yet, there has been no clear strategy formulated in which a patient's own tumor tissues is used to generate an antitumor adaptive immune response for the eradication of metastases and prevention of relapse. Once tumors metastasize, curing the disease is difficult and rare. This review summarizes recent findings supporting the hypothesis that targeting primary tumors with both conventional and new therapies can potentially generate antitumor adaptive immune responses that prevent metastases and relapse.Due to the vast number of genetic changes associated with carcinogenesis, tumors express many neo-antigens and mutated antigens. Indeed, much evidence exists to indicate that many cancers are antigenic and thus recognizable by the adaptive immune system. 2 Mere recognition by adaptive immunity, however, is insufficient, given that these antigenic cancers rarely regress spontaneously. Effective antitumor immunity depends on both the presence of tumor-reactive lymphocyte precursors and means by which these precursor lymphocytes can be activated. Most T cells with high affinity to tissue-specific antigens are deleted in the thymus or later tolerized in the peripheral

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Antigen Bias in T Cell Cross-Priming

Cited by 171 publications

References 25 publications

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Targeting and utilizing primary tumors as live vaccines: changing strategies

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