Pathways of MHC I cross-presentation of exogenous antigens

Cruz, Freidrich M.; Chan, Amanda; Rock, Kenneth L.

doi:10.1016/j.smim.2023.101729

Cited by 23 publications

(15 citation statements)

References 203 publications

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“…XP is important for the generation of many virus-and tumour-specific CTL responses [1][2][3][4][5][6][7][8] . Despite its obvious biological importance, the mechanism(s) by which XP is achieved remain unclear 10,19,63,[76][77][78][79] . Two recent observations from the XP literature informed the present study.…”

Section: Discussionmentioning

confidence: 99%

The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells

Gonzales,

Huang,

Rajwani

et al. 2023

Preprint

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Type I conventional dendritic cells (cDC1s) are essential for the generation of protective cytotoxic T lymphocyte (CTL) responses against many types of viruses and tumours. They do so by internalizing antigens from virally infected or tumour cells and presenting them to CD8+ T cells in a process known as cross-presentation (XP). Despite the obvious biological importance of XP, the molecular mechanism(s) driving this process remain unclear. Here, we show that a cDC-specific pore-forming protein called apolipoprotein 7C (APOL7C) is upregulated in response to innate immune stimuli and is recruited to phagosomes. Strikingly, the association of APOL7C with phagosomes leads to phagosomal rupture, which in turn allows for the escape of engulfed protein antigens to the cytosol where they can be processed via the endogenous major histocompatibility complex (MHC) class I antigen processing pathway. We show that APOL7C recruitment to phagosomes is voltage-dependent and occurs in response to NADPH oxidase-induced depolarization of the phagosomal membrane. Our data indicate the presence of dedicated pore-forming apolipoproteins that mediate the delivery of phagocytosed proteins to the cytosol of activated cDC1s to facilitate MHC class I presentation of exogenous antigen and to regulate adaptive immunity.

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Section: Discussionmentioning

confidence: 99%

The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells

Gonzales,

Huang,

Rajwani

et al. 2023

Preprint

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“…HLA-I genes can be divided into three classical groups (HLA-A, HLA-B and HLA-C) or the non-classical groups (for example, HLA-E, HLA-F and HLA-G) (11). HLA-I molecules are composed of a heavy chain (the α-chain) and a light chain (the β2m chain) (12). The α-chain is encoded by HLA-A, B and C alleles, and is divided into the extracellular, transmembrane and intracellular regions (12).…”

Section: Physiological Function and Structure Of Hlamentioning

confidence: 99%

“…HLA-I molecules are composed of a heavy chain (the α-chain) and a light chain (the β2m chain) (12). The α-chain is encoded by HLA-A, B and C alleles, and is divided into the extracellular, transmembrane and intracellular regions (12). The extracellular region of the α-chain is formed by the folding of the three functional regions (namely, α1, α2 and α3), where CD8 binding sites are located on α3 (12).…”

Section: Physiological Function and Structure Of Hlamentioning

confidence: 99%

“…The α-chain is encoded by HLA-A, B and C alleles, and is divided into the extracellular, transmembrane and intracellular regions (12). The extracellular region of the α-chain is formed by the folding of the three functional regions (namely, α1, α2 and α3), where CD8 binding sites are located on α3 (12). By contrast, the β2m chain, encoded by the β2 microglobulin gene, is attached to the α3 region by non-covalent bonds (13).…”

Section: Physiological Function and Structure Of Hlamentioning

confidence: 99%

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Human leukocyte antigen and tumor immunotherapy (Review)

Liu

Mou²,

et al. 2023

Int J Oncol

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Malignant tumors seriously endanger human health and life, and restrict economic development. Human leukocyte antigen (HLA) is the expression product of the human major histocompatibility complex, which, at present, is the most complex known polymorphic system. The polymorphism and expression of HLA molecules have been demonstrated to be associated with the occurrence and development of tumors. HLA molecules can regulate the proliferation of tumor cells and inhibit antitumor immunity. In the present review, the structure and function of HLA molecules, the polymorphism and expression of HLA in tumor tissue, the roles of HLA in tumor cells and tumor immunity, and the potential clinical application of HLA in tumor immunotherapy are summarized. The overall aim of the present review is to provide relevant information for the development of antitumor immunotherapies involving HLA in the clinic. Contents 1. Introduction 2. Physiological function and structure of HLA 3. HLA polymorphism and cancer 4. Function of HLA in tumor immunity 5. Clinical significance of HLA in tumor immunotherapy 6. Future perspectives

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“…It has been known that Class I MHC (MHC-I) molecules present primarily endogenous antigens, i.e. antigens that are present in the cytosol and are subject to the cytosolic processing mechanisms that comprise the conventional MHC-I processing pathway, which plays important roles in generating CD8 T cell responses [29]. After phagocytic or endocytic uptake, some exogenous antigens can escape the vacuolar system and penetrate into the cytosol, accessing the conventional MHC-I antigen processing mechanisms [30].…”

Section: Introductionmentioning

confidence: 99%

Potentiating humoral and cellular immunity using a novel hybrid polymer-lipid nanoparticle adjuvant for HBsAg-VLP vaccine

Liu

Min

Song

et al. 2023

Preprint

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Aluminum adjuvants are commonly used in vaccines to stimulate the immune system, but they have limited ability to promote cellular immunity which is necessary for clearing viral infections like hepatitis B. Current adjuvants that do promote cellular immunity often have undesired side effects due to the immunostimulants they contain. In this study, a hybrid polymer lipid nanoparticle (HPLNP) was developed as an efficient adjuvant for the hepatitis B surface antigen (HBsAg) virus-like particle (VLP) vaccine to potentiate both humoral and cellular immunity. The HPLNP is composed of FDA approved polyethylene glycol-b-poly (L-lactic acid) (PEG-PLLA) polymer and cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and can be easily prepared by a one-step method. The cationic optimised vaccine formulation HBsAg/HPLNP (w/w = 1/600) can maximise the cell uptake of the antigen due to the electrostatic adsorption between the vaccine nanoparticle and the cell membrane of antigen-presenting cells. The HPLNP prolonged the retention of the antigen at the injection site and enhanced the lymph node drainage of antigen, resulting in a higher concentration of serum anti-HBsAg IgG compared to the HBsAg group or the HBsAg/Al group after the boost immunisation in mice. The HPLNP also promoted a strong Th1-driven immune response, as demonstrated by the significantly improved IgG2a/IgG1 ratio, increased production of IFN-γ, and activation of CD4 + and CD8 + T cells in the spleen and lymph nodes. Importantly, the HPLNP demonstrated no systemic toxicity during immunisation. The advantages of the HPLNP, including good biocompatibility, easy preparation, low cost, and its ability to enhance both humoral and cellular immune responses, suggest its suitability as an efficient adjuvant for protein-based vaccines such as HBsAg-VLP. These findings highlight the promising potential of the HPLNP as an HBV vaccine adjuvant, offering an alternative to aluminum adjuvants currently used in vaccines.

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Pathways of MHC I cross-presentation of exogenous antigens

Cited by 23 publications

References 203 publications

The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells

The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells

Human leukocyte antigen and tumor immunotherapy (Review)

Potentiating humoral and cellular immunity using a novel hybrid polymer-lipid nanoparticle adjuvant for HBsAg-VLP vaccine

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