Hepatitis B virus small surface antigen particles are processed in a novel endosomal pathway for major histocompatibility complex class I‐restricted epitope presentation

Schirmbeck, Reinhold; Melber, Karl; Reimann, Jörg

doi:10.1002/eji.1830250431

Cited by 136 publications

(100 citation statements)

References 45 publications

(18 reference statements)

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“…Although the present experiments do not exclude that any cross-priming can take place [e.g., in the BM chimeras (17) or for high dosed antigens (5,6,(8)(9)(10)(11)], our results nevertheless render cross-priming of antiviral CTL responses too inefficient or insufficient to be generalized as an important physiological process.…”

Section: Discussioncontrasting

confidence: 61%

Endogenous neosynthesis vs. cross-presentation of viral antigens for cytotoxic T cell priming

Freigang

Egger

Bienz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Induction of antiviral cytotoxic T lymphocytes (CTLs) has been proposed to require cross-presentation of viral antigens derived from infected extralymphatic host cells by antigen-presenting cells (APC). This postulated mechanism of cross-priming is thought to be essential for CTL responses against viruses that do not infect professional APC, e.g., because of absence of the specific virus receptor. Here, we show for the human pathogen poliovirus that naturally nonpermissive murine APC acquire viral RNA in vivo independently of the cellular virus receptor. Uptake of poliovirus or polioviral RNA initiated neosynthesis of viral antigen to an extent sufficient to prime CTLs in vivo, which were detectable 2-3 wk after infection. Our results do not only indicate that experiments studying cross-presentation and cross-priming by using potentially amplifiable or translatable materials need careful examination, but they also question the general biological importance of cross-presentation and cross-priming in antiviral CTL responses.

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Section: Discussioncontrasting

confidence: 61%

Endogenous neosynthesis vs. cross-presentation of viral antigens for cytotoxic T cell priming

Freigang

Egger

Bienz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…In one pathway, exogenous antigens gain access to the cytosol and are presented in a TAP-dependent manner (12,13,14,17). The other pathway is non-cytosolic, and presentation is mostly TAP independent (16,43). In our study, we have shown that bacterial OVA is processed via a TAP-dependent mechanism, indicating a classical loading of MHC class I molecules.…”

Section: Discussionmentioning

confidence: 59%

“…We have previously shown that, similarly to macrophages (12)(13)(14)(15)(16), cloned DC can efficiently process exogenous viral proteins for class I presentation to cytotoxic T cells (11). However, soluble proteins are very poorly presented on MHC class I molecules through a mechanism that is TAP dependent (17).…”

mentioning

confidence: 99%

Bacteria-induced neo-biosynthesis, stabilization, and surface expression of functional class I molecules in mouse dendritic cells

Rescigno

Citterio

Théry

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

227

188

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Here, we show that bacteria induce de novo synthesis of both major histocompatability complex (MHC) class I and II molecules in a mouse dendritic cell culture system. The neo-biosynthesis of MHC class I molecules is delayed as compared with that of MHC class II. Furthermore, bacteria stabilize MHC class I molecules by a 3-fold increase of their half-life. This has important consequences for the capacity of dendritic cells to present bacterial antigens in the draining lymph nodes. In addition, a model antigen, ovalbumin, expressed on the surface of recombinant Streptococcus gordonii is processed and presented on MHC class I molecules. This presentation is 10 6 times more efficient than that of soluble OVA protein. This exogenous pathway of MHC class I presentation is transporter associated with antigen processing (TAP)-dependent, indicating that there is a transport from phagolysosome to cytosol in dendritic cells. Thus, bacteria are shown to be a potentially useful mean for the correct delivery of exogenous antigens to be presented efficiently on MHC class I molecules.

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“…The empty MHC class I molecules that bind peptides from exogenous Ags in endosomal compartments are derived from MHC class I molecules that have lost their endogenous peptides either within the endosomal compartment or on the cell surface before endocytosis. Interestingly, L d has been shown to participate in these alternative pathways (46,47) either by binding regurgitated peptides on the cell surface or via internalization of open forms from the cell surface. While other MHC class I molecules can also participate in these pathways (17,45,48), the comparative instability of trimeric L d -peptide-␤ 2 m complexes may allow L d to use these pathways more efficiently.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism at Position 97 in MHC Class I Molecules Affects Peptide Specificity, Cell Surface Stability, and Affinity for β2-Microglobulin

Smith

Myers

Robinson

et al. 2002

The Journal of Immunology

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The two mouse MHC class I alleles, Ld and Lq, share complete amino acid sequence identity except in the α2 domain, where they differ at six positions. Despite their similarity, Lq has a stronger association with β2-microglobulin (β2m), is expressed at higher levels on the cell surface, demonstrates an increased cell surface half-life, and has fewer open forms on the cell surface than Ld. To determine the basis for their phenotypic differences, Ld molecules containing chimeric Ld-Lq α2 domains were characterized, and these analyses implicated residue 97 (LdTrp and LqArg) as the polymorphic site responsible for the disparity in β2m association between the two alleles. Single substitution analysis at this site (LdW97R and LqR97W) confirmed this. Furthermore, the LdW97R mutant molecule has a longer cell surface half-life than either Lq or Ld, and fewer open forms of LdW97R are observed on the cell surface. In addition, both LdW97R and Lq possess decreased binding affinity for the Ld-restricted tum− P91A14–22 peptide compared with Ld. Collectively, these results and the known location of Trp97 in the peptide binding cleft of Ld strongly suggest that the substitution of Arg for Trp97 in Ld alters the peptide binding cleft, increasing its affinity for endogenous peptides, which results in greater cell surface stability and better retention of β2m. Furthermore, these results imply that Trp97 plays an important role in the ability of Ld to efficiently participate in alternative MHC class I Ag presentation pathways.

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Hepatitis B virus small surface antigen particles are processed in a novel endosomal pathway for major histocompatibility complex class I‐restricted epitope presentation

Cited by 136 publications

References 45 publications

Endogenous neosynthesis vs. cross-presentation of viral antigens for cytotoxic T cell priming

Endogenous neosynthesis vs. cross-presentation of viral antigens for cytotoxic T cell priming

Bacteria-induced neo-biosynthesis, stabilization, and surface expression of functional class I molecules in mouse dendritic cells

Polymorphism at Position 97 in MHC Class I Molecules Affects Peptide Specificity, Cell Surface Stability, and Affinity for β2-Microglobulin

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