Antigen Processing and Presentation
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Questions and Answers

Which molecule is responsible for transporting peptides across the endoplasmic reticulum in antigen processing?

  • Proteasome
  • Calnexin
  • Invariant Chain
  • TAP Transporter (correct)

    • What is the primary function of the proteasome in antigen processing?

  • Binding peptides to MHC class I molecules
  • Stabilizing MHC class II molecules
  • Degrading cytosolic proteins into peptides (correct)
  • Transporting peptides across the ER

    • What is the role of the invariant chain (Ii) in MHC class II processing?

  • To assist in peptide binding
  • To prevent premature peptide binding in the ER (correct)
  • To transport peptides to the ER
  • To trim peptides to the correct length

    • Which component serves as a chaperone protein for MHC class I molecules in the ER?

    <p>Calnexin (D)</p> Signup and view all the answers

    Which pathway processes intracellular antigens and is associated with MHC class I?

    <p>Endogenous pathway (B)</p> Signup and view all the answers

    What role does ERAAP play in antigen processing?

    <p>It trims peptides to the correct length (D)</p> Signup and view all the answers

    Which of the following correctly describes MHC class II processing?

    <p>It processes extracellular antigens (D)</p> Signup and view all the answers

    Which component links MHC class I molecules to the TAP during peptide loading?

    <p>Tapasin (C)</p> Signup and view all the answers

    Flashcards

    Proteasome

    A large, multicatalytic protease complex responsible for degrading proteins within the cytosol. It is composed of approximately 28 subunits.

    TAP Transporter (Transporter Associated with Antigen Processing)

    A heterodimer composed of TAP-1 and TAP-2 proteins that transports peptides across the endoplasmic reticulum (ER). It plays a crucial role in the MHC Class I antigen processing pathway.

    Calnexin

    An ER membrane-bound chaperone protein that binds to MHC Class I molecules until a peptide is loaded onto it. This ensures that only peptide-loaded MHC Class I molecules are transported to the cell surface.

    Peptide Loading Complex (PLC)

    A complex of chaperone proteins (calreticulin, tapasin, ERp57) that facilitates the loading of peptides onto MHC Class I molecules in the ER.

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    ERAAP (Endoplasmic Reticulum Aminopeptidase associated with Antigen Processing)

    An enzyme that trims the ends of peptides, ensuring they are the correct length for binding to MHC Class I molecules.

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    Invariant Chain (Ii, CD74)

    Associated with MHC Class II molecules, this invariant chain acts like a placeholder, preventing peptide binding in the ER. It guides MHC Class II molecules to low pH endosomes where they encounter exogenous antigens.

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    Endogenous Pathway

    The process by which intracellular antigens are processed and presented on MHC Class I molecules to CD8+ T cells. This pathway involves proteasome degradation, TAP transport, and peptide loading in the ER.

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    Exogenous Pathway

    The process by which extracellular antigens are processed and presented on MHC Class II molecules to CD4+ T cells. This pathway involves antigen uptake, processing in endosomes, and peptide loading in the ER and endosomes.

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    Study Notes

    Antigen Processing and Presentation

    • Antigen processing involves two main pathways: MHC class I and MHC class II

    • The endogenous pathway (MHC class I): processes intracellular antigens

      • Intracellular proteins are degraded into peptides by the proteasome.
      • Peptides are transported into the endoplasmic reticulum via TAP.
      • Peptides bind to MHC class I molecules.
      • MHC class I-peptide complexes are presented on the cell surface to CD8+ T cells.

    • The exogenous pathway (MHC class II): processes extracellular antigens

      • Extracellular antigens are taken up by endocytosis, forming endosomes or lysosomes.
      • Antigens are degraded to peptides.
      • Peptides bind to MHC class II molecules.
      • MHC class II-peptide complexes are presented on the cell surface to CD4+ T cells.

    Processing "Machinery"

    • Proteasome: A large, multicatalytic protease complex (~28 subunits) that degrades cytosolic proteins.
    • TAP Transporter (transporter associated with antigen processing): A heterodimer of TAP-1 and TAP-2 proteins.
      • Transports peptides across the endoplasmic reticulum (ER).
    • Calnexin: An ER membrane-bound protein (88 kDa) that retains MHC class I molecules in the ER until the peptide is bound. It acts as a chaperone protein.
    • Peptide Loading Complex (PLC): A complex of chaperone proteins
      • Calreticulin: Similar function to calnexin
      • Tapasin: Links MHC Class I to TAP.
      • ERp57: Mediates peptide binding to Class I.
    • Endoplasmic Reticulum Aminopeptidase associated with Antigen Processing (ERAAP): Trims peptides to the correct length.

    Invariant Chain (Ii, CD74)

    • Associates with newly formed MHC class II molecules to prevent peptide binding in the ER.
    • Targets delivery of new Class II molecules to low pH endosomes.

    Antigen Processing with Class I

    • Partly folded MHC class I α chains bind to calnexin until β2-microglobulin binds.
    • MHC class I α:β2m complex is released from calnexin.
    • Binds a complex of chaperone proteins (calreticulin, ERp57) and TAP via tapasin.
    • Cytosolic proteins (and defective ribosomal products) are degraded to peptide fragments by the proteasome.
    • TAP delivers peptides to the ER.
    • A peptide binds MHC class I molecule and completes its folding.
    • The MHC class I molecule is released from the TAP complex and exported to the cell membrane.
    • Normal proteins (>70%) vs. DRIPs (<30%).

    Antigen Processing with Class II

    • Invariant chain (li, CD74) forms a complex with MHC class II molecules blocking peptide binding and misfolded protein binding.
    • li is cleaved in an acidified endosome; leaving a short peptide fragment (CLIP) still bound to MHC class II.
    • Endocytosed antigens are degraded to peptides in endosomes; CLIP blocks antigen binding to MHC II.
    • HLA-DM binds to MHC II molecule, releasing CLIP, allowing other peptides to bind.
    • MHC II molecule travels to the cell surface.

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    Antigen Processing and Presentation (University of Portsmouth)

    Description

    This quiz explores the intricate processes of antigen processing through the MHC class I and II pathways. Understand how intracellular and extracellular antigens are presented to T cells and the role of key elements like proteasomes and TAP transporters in these mechanisms. Test your knowledge on the fundamentals of immunology.

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