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Immune response Antigen presentation by MHC class I


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Immune response Antigen presentation by MHC class I

Antigen presentation by MHC class I

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

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

Expression of MHC molecules is constitutively activated during development inprofessional 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 endogenouslysynthesized proteins, including self-proteins and viral proteins synthesized in host uponinfection to TCR of CD8+ T-cells. Intracellular proteins are degraded intoantigenic peptides by the 26S proteasome and transported into endoplasmicreticulum (ER) via TAP1 and TAP2 transporters. MHC class I moleculesare tethered to TAP transporter via TAP-binding protein, Tapasin. MHC classI heavy chains bind ER chaperone calnexin. Upon folding, they dissociate fromcalnexin and bind beta-2 microglobulin, ER chaperone calreticulinand thiol oxodoreductase PDIA3. Then, MHC class I proteins bind antigenicpeptides.

MHC class I -peptide complex is transported to cell surface for presentation toCD8+ T-cells [1]. MHC class I heavy chains that fail to acquire amature conformation in ER as a result of defective folding or assembly withBeta-2-microglobulin, are retranslocated via Sec61 channel to cytosol fordegradation by proteasome [2].