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Empty MHC class I molecules come out in the cold

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TLDR
It is reported here that culture of the murine lymphoma mutant cell line RMA-S at reduced temperature promotes assembly, and results in a high level of cell surface expression of H-2/β2-microglobulin complexes that do not present endogenous antigens, and are labile at 37 °C.
Abstract
Major histocompatibility complex (MHC) class I molecules present antigen by transporting peptides from intracellularly degraded proteins to the cell surface for scrutiny by cytotoxic T cells. Recent work suggests that peptide binding may be required for efficient assembly and intracellular transport of MHC class I molecules, but it is not clear whether class I molecules can ever assemble in the absence of peptide. We report here that culture of the murine lymphoma mutant cell line RMA-S at reduced temperature (19-33 degrees C) promotes assembly, and results in a high level of cell surface expression of H-2/beta 2-microglobulin complexes that do not present endogenous antigens, and are labile at 37 degrees C. They can be stabilized at 37 degrees C by exposure to specific peptides known to interact with H-2Kb or Db. Our findings suggest that, in the absence of peptides, class I molecules can assemble but are unstable at body temperature. The induction of such molecules at reduced temperature opens new ways to analyse the nature of MHC class I peptide interactions at the cell surface.

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Citations
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Journal ArticleDOI

Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.

TL;DR: It is shown that the processing of CFTRΔF508 reverts towards that of wild-type as the incubation temperature is reduced, and when the processing defect is corrected, cAMP-regulated Cl− channels appear in the plasma membrane.
Journal ArticleDOI

Mechanisms of mhc class i-restricted antigen processing

TL;DR: A subset of the proteasome beta-subunits and one of the accessory complexes are upregulated by gamma-interferon and affect the generation of peptides to promote more efficient antigen recognition and bind lipid-based ligands within the endocytic pathway.
Journal ArticleDOI

The biochemistry and cell biology of antigen processing and presentation

TL;DR: The importance of conformational changes accompanying peptide binding that affect subunit stability of MHC molecules, and the relationship between these changes and the handling of proteins by intracellular chaperones, are emphasized as key features in the operation of the class I and class II presentation pathways.
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Identification of self peptides bound to purified HLA-B27.

TL;DR: Self peptides derive from abundant cytosolic or nuclear proteins, such as histone, ribosomal proteins, and members of the 90K heat-shock protein family, and match to protein sequences in a database search.
Journal ArticleDOI

Herpes simplex virus turns off the TAP to evade host immunity

TL;DR: It is shown here that ICP47 binds to TAP and prevents peptide translocation into the endoplasmic reticulum.
References
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Journal ArticleDOI

In search of the 'missing self': MHC molecules and NK cell recognition.

TL;DR: In vivo studies with H-2-deficient targets that support the 'missing self' hypothesis are reviewed and testable predictions for how MHC class I molecules act in cases where they control a rate-limiting step in the NK cell-target interaction are derived.
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Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy

TL;DR: It is shown that murine lymphoma cells selected for loss of H–2 expression are less malignant after low-dose inoculation in syngeneic hosts than are wild-type cells, and that the rejection of such cells is non-adaptive.
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The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides

TL;DR: The authors showed that the epitopes of nucleoprotein recognized by CTL in association with class I molecules of the major histocompatibility complex in both mouse and man can be defined with short synthetic peptides derived from the nucleopprotein sequence.
Journal ArticleDOI

Association of class I major histocompatibility heavy and light chains induced by viral peptides.

TL;DR: A cell in which association of a major histocompatibility complex class I heavy chain with β2-microglobulin is induced by a peptide derived from influenza nucleoprotein is described.
Journal ArticleDOI

Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism.

TL;DR: The reduced tumorigenicity of sublines with impaired H-2 expression is largely, if not exclusively due to rapid elimination by NK cells, which may reflect an inverse, indirect relation between factors controlling H- 2 expression and NK sensitivity.
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