Cross-presentation of exogenous antigens on MHC I molecules

Colbert, Jeff D.; Cruz, Freidrich M.; Rock, Kenneth L.

doi:10.1016/j.coi.2019.12.005

Cited by 101 publications

(70 citation statements)

References 99 publications

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“…In contrast, protein antigens that are picked up from the extracellular space are poorly presented to CD8 T cells. The one exception to this rule is in small fractions of dendritic cells that are capable of so-called cross-presentation, i.e., the cellular uptake of extracellular protein (especially particulate antigens) and the presentation of processed peptides on HLA class I molecules to CD8 T cells [69]. Cross-presentation is rather slow and often rate limiting, which is a major reason why full-length protein vaccines are inefficient for inducing CD8 T cell responses.…”

Section: T Cell Targetsmentioning

confidence: 99%

COVID-19: Mechanisms of Vaccination and Immunity

2020

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Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy.

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Section: T Cell Targetsmentioning

confidence: 99%

COVID-19: Mechanisms of Vaccination and Immunity

2020

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“…NPs bound with antigens/adjuvants are internalized through endocytosis, and if the antigens are not released from the endosomes into cytosol, they present the antigens to the MHC-II pathway and activate the CD4 + T cells (Tran et al, 2018 ). Therefore, for effective immunotherapy, antigen should be bound with MHC-I molecules which requires the release of antigen into cytosol and formation of antigen-MHC-I complex within endoplasmic reticulum to activate CD8 + T cells (Colbert et al, 2020 ). Stimulation of DCs can be achieved either through passive targeting by directing antigen-loaded NPs toward sites that are rich in DCs or by active targeting.…”

Section: Strategies For Immunostimulatory Nanoparticles In Cancer Immmentioning

confidence: 99%

Nanoparticles as Smart Carriers for Enhanced Cancer Immunotherapy

Thakur

Chatterjee

et al. 2020

Front. Chem.

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Cancer immunotherapy has emerged as a promising strategy for the treatment of many forms of cancer by stimulating body's own immune system. This therapy not only eradicates tumor cells by inducing strong anti-tumor immune response but also prevent their recurrence. The clinical cancer immunotherapy faces some insurmountable challenges including high immune-mediated toxicity, lack of effective and targeted delivery of cancer antigens to immune cells and off-target side effects. However, nanotechnology offers some solutions to overcome those limitations, and thus can potentiate the efficacy of immunotherapy. This review focuses on the advancement of nanoparticle-mediated delivery of immunostimulating agents for efficient cancer immunotherapy. Here we have outlined the use of the immunostimulatory nanoparticles as a smart carrier for effective delivery of cancer antigens and adjuvants, type of interactions between nanoparticles and the antigen/adjuvant as well as the factors controlling the interaction between nanoparticles and the receptors on antigen presenting cells. Besides, the role of nanoparticles in targeting/activating immune cells and modulating the immunosuppressive tumor microenvironment has also been discussed extensively. Finally, we have summarized some theranostic applications of the immunomodulatory nanomaterials in treating cancers based on the earlier published reports.

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“…Thus, direct presentation correlates with the rate of protein translation and proteasomal degradation, whereas cross-presentation correlates with steady-state protein amounts [83]. APCs acquire proteins from donor cells (e.g., cancer cells) through endocytic mechanisms, of which the most efficient is phagocytosis [84]. Internalized proteins can then be degraded by proteasomes, either in endocytic organelles or in the cytosol [84,85].…”

Section: Cross-presentation Yields a Biased Representation Of The Tsamentioning

confidence: 99%

“…APCs acquire proteins from donor cells (e.g., cancer cells) through endocytic mechanisms, of which the most efficient is phagocytosis [84]. Internalized proteins can then be degraded by proteasomes, either in endocytic organelles or in the cytosol [84,85]. A key implication is that cross-presentation can only display a fraction of TSAs, that is, TSAs derived from highly abundant and stable proteins.…”

Section: Cross-presentation Yields a Biased Representation Of The Tsamentioning

confidence: 99%

The Origin and Immune Recognition of Tumor-Specific Antigens

Apavaloaei

Hardy

Thibault

et al. 2020

Preprint

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The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

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Cross-presentation of exogenous antigens on MHC I molecules

Cited by 101 publications

References 99 publications

COVID-19: Mechanisms of Vaccination and Immunity

COVID-19: Mechanisms of Vaccination and Immunity

Nanoparticles as Smart Carriers for Enhanced Cancer Immunotherapy

The Origin and Immune Recognition of Tumor-Specific Antigens

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