Immune response - Antigen presentation by MHC class I

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Antigen presentation by MHC class I

Antigen processing and presentation is the process by which antigen-presenting cells express antigen on their cell surface in a form recognizable by lymphocytes.

Antigen processing includes protein fragmentation (proteolysis), association of the fragments with MHC (major histocompatibility complex), and expression of the peptide-MHC complex at the cell surface where they can be recognized by the T cell receptor (TCR) on a T cell.

Expression of MHC molecules is constitutively activated during development in professional antigen-presenting cells, such as B cells, dendritic cells and macrophages. There are two classes of MHC proteins, MHC class I and MHC class II.

MHC class I molecules are specialized for presentation of endogenously synthesized proteins, including self-proteins and viral proteins synthesized in host upon infection, to TCR of CD8+ T-cells. Intracellular proteins are degraded into antigenic peptides by the 26S proteasome and transported into endoplasmic reticulum (ER) via TAP1 and TAP2 transporters. MHC class I molecules are tethered to TAP transporter via TAP-binding protein, Tapasin. MHC class I heavy chains bind ER chaperone calnexin. Upon folding, they dissociate from calnexin and bind beta-2 microglobulin, ER chaperone calreticulin and thiol oxodoreductase PDIA3. Then, MHC class I proteins bind antigenic peptides.

MHC class I-peptide complex is transported to cell surface for presentation to CD8+ T-cells [1]. MHC class I heavy chains that fail to acquire a mature conformation in ER as a result of defective folding or assembly with Beta-2-microglobulin, are retranslocated via Sec61 channel to cytosol for degradation by proteasome [2].

References:

  1. Cresswell P, Ackerman AL, Giodini A, Peaper DR, Wearsch PA
    Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunological reviews 2005 Oct;207:145-57
  2. Albring J, Koopmann JO, Hammerling GJ, Momburg F
    Retrotranslocation of MHC class I heavy chain from the endoplasmic reticulum to the cytosol is dependent on ATP supply to the ER lumen. Molecular immunology 2004 Jan;40(10):733-41

  1. Cresswell P, Ackerman AL, Giodini A, Peaper DR, Wearsch PA
    Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunological reviews 2005 Oct;207:145-57
  2. Albring J, Koopmann JO, Hammerling GJ, Momburg F
    Retrotranslocation of MHC class I heavy chain from the endoplasmic reticulum to the cytosol is dependent on ATP supply to the ER lumen. Molecular immunology 2004 Jan;40(10):733-41

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