Stability of Surface H-2Kb, H-2Db, and Peptide-Receptive H-2Kb on Splenocytes

Su, Ruey-Chyi; Miller, Richard G.

doi:10.4049/jimmunol.167.9.4869

Cited by 30 publications

(23 citation statements)

References 60 publications

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“…Biexponential fits yielded much better approximations to the data (Fig. 5A, thick line), as was previously reported in a study of the surface stability of the mouse class I MHC molecule, H-2K b (41).…”

Section: Overexpression Of Bap31 Increases the Stability Of Surface Csupporting

confidence: 59%

Bap31 Enhances the Endoplasmic Reticulum Export and Quality Control of Human Class I MHC Molecules

Ladasky

Boyle

Seth

et al. 2006

The Journal of Immunology

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The assembly of class I MHC molecules and their export from the endoplasmic reticulum (ER) is governed by chaperones and accessory proteins. We present evidence that the putative cargo receptor protein Bap31 participates in the transport and the quality control of human class I molecules. Transfection of the human adenocarcinoma cell line HeLa with yellow fluorescent protein-Bap31 chimeras increased surface levels of class I in a dose-dependent manner, by as much as 3.7-fold. The increase in surface class I resulted from an increase in the rate of export of newly synthesized class I molecules to the cell surface and from an increase in the stability of the exported molecules. We propose that Bap31 performs quality control on class I molecules in two distinct phases: first, by exporting peptide-loaded class I molecules to the ER/Golgi intermediate compartment, and second, by retrieving class I molecules that have lost peptides in the acidic post-ER environment. This function of Bap31 is conditional or redundant, because we find that Bap31 deficiency does not reduce surface class I levels. Overexpression of the Bap31 homolog, Bap29, decreases surface class levels in HeLa, indicating that it does not substitute for Bap31.

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Section: Overexpression Of Bap31 Increases the Stability Of Surface Csupporting

confidence: 59%

Bap31 Enhances the Endoplasmic Reticulum Export and Quality Control of Human Class I MHC Molecules

Ladasky

Boyle

Seth

et al. 2006

The Journal of Immunology

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“…This high potency is generally attributed to accessory signals provided by DC, which include the expression of costimulatory molecules, adhesion molecules, chemokines and cytokines, as well as to a high efficiency of antigen uptake, processing and presentation [5,6]. With a few exceptions [7][8][9][10], the impact of these factors and processes have been analyzed by measuring responses of T cells with specificity for the epitope of interest [11,12], protection against infection [13], induction of autoimmune responses [14] or rejection of transplantation tumors [15][16][17]. These studies could establish that different modes of antigen loading result in different efficiencies of T cell stimulation and that different epitopes may confer different half-life times of their complexes with the MHC molecules.…”

Section: Introductionmentioning

confidence: 99%

Extended presentation of specific MHC‐peptide complexes by mature dendritic cells compared to other types of antigen‐presenting cells

et al. 2004

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Dendritic cells are known as the most potent antigen-presenting cells for the induction of T cell-mediated immune responses. To discriminate between the presentation of antigens and the co-stimulatory aspects of this high immunostimulatory capacity, we used recombinant antibodies with T cell receptor-like specificity to detect defined MHC-peptide complexes on living cells. Mature human dendritic cells (mDC) were compared with immature DC (iDC), monocytes, CD4 + T lymphocytes, melanoma cells, T2 cells and B lymphoblastoid cells for their capacity to present MHC class I-restricted tumor-associated T cell epitopes and were found to display the specific peptides two to six times longer than other cells. The most short-lived peptide had an average half-life of 8.7 h on mDC vs. 3.5 h on B lymphoblastoid cells, while the most long-lived peptide had a half-life of 118.5 h vs. 20.7 h on these two cell types. The decay kinetics of specific MHC-peptide complexes on iDC were among the fastest observed. The high potency of dendritic cells to induce specific T cell responses is thus based, in addition to the expression of co-stimulatory molecules, on an extended antigenic memory, which increases the likelihood and the extent of contacts between dendritic cells and antigen-specific T cells.

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“…The dynamics of intracellular (endogenous) peptide production and their association with MHC have been extensively examined (10,11,12) (SI Text, R9), and the thermodynamics and kinetics of some pMHC interactions have been characterized in considerable detail (13)(14)(15). Still, although peptide pulsing is indispensable for efforts to identify peptides recognized by T cells, the binding of extracellular peptides to cell surface MHC is not sufficiently wellunderstood to predict the number of pMHCs formed on cells after exposing them to an extracellular peptide.…”

mentioning

confidence: 99%

Promiscuous binding of extracellular peptides to cell surface class I MHC protein

Eisen

Hou

Shen

et al. 2012

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

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Algorithms derived from measurements of short-peptide (8-10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K b , can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide-MHC complexes that form on cells exposed to extracellular (exogenous) peptides.

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Stability of Surface H-2Kb, H-2Db, and Peptide-Receptive H-2Kb on Splenocytes

Cited by 30 publications

References 60 publications

Bap31 Enhances the Endoplasmic Reticulum Export and Quality Control of Human Class I MHC Molecules

Bap31 Enhances the Endoplasmic Reticulum Export and Quality Control of Human Class I MHC Molecules

Extended presentation of specific MHC‐peptide complexes by mature dendritic cells compared to other types of antigen‐presenting cells

Promiscuous binding of extracellular peptides to cell surface class I MHC protein

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