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MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
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Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
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The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
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Export of Misfolded Proteins out of the ER01:32

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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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Lysosomal Hydrolases01:22

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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Major histocompatibility complex class I assembly within endolysosomal pathways.

Eli Olson1, Malini Raghavan2

  • 1Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Medicine, Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Graduate Program In Immunology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

Current Opinion in Immunology
|June 28, 2023
PubMed
Summary
This summary is machine-generated.

Major histocompatibility complex class I (MHC class I) molecules present peptides for immune surveillance. This study reveals MHC class I also assembles peptides within endosomes, influenced by human genetic variations.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Major histocompatibility complex class I (MHC class I) molecules are crucial for cellular immune surveillance, presenting peptides on the cell surface.
  • MHC class I assembly typically occurs in the endoplasmic reticulum (ER) after peptide processing in the cytosol.
  • Pathogen evasion strategies necessitate peptide sampling from various subcellular compartments, including endosomes.

Purpose of the Study:

  • To investigate the role of endosomes in MHC class I assembly.
  • To explore how MHC class I molecules interact with exogenous and endogenous antigens within endosomes.
  • To determine the influence of human MHC class I polymorphisms on endosomal assembly.

Main Methods:

  • Analysis of MHC class I trafficking between cell surface and endosomes.
  • Investigating peptide loading onto MHC class I within endosomal compartments.
  • Examining the impact of specific MHC class I polymorphisms on endosomal assembly.

Main Results:

  • MHC class I molecules are shown to assemble with peptides within endosomal compartments.
  • Both exogenous and endogenous antigens are processed and presented by MHC class I in endosomes.
  • Human MHC class I polymorphisms affect endosomal assembly, similar to their known effects on ER assembly.

Conclusions:

  • Endosomes represent an important site for MHC class I assembly and peptide loading, in addition to the ER.
  • The findings highlight the plasticity of MHC class I assembly pathways in response to cellular compartmentalization.
  • Understanding endosomal MHC class I assembly, particularly its modulation by genetic polymorphisms, is critical for advancing immunology and disease research.