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Mechanisms of Antigen Processing For Class I MHC Presentation
Mechanisms of Antigen Processing For Class I MHC Presentation
Antigen Processing
Antigen Processing:
Create
peptides from native proteins, prepares antigens for presentation to cells of immune system (T lymphoctyes) Stage of antigen presentation pathways
Antigen Presentation:
Display
Basic Overview
Cytosolic protein degradation by proteasome (catalytic core and regulatory caps) Hollow core with active proteolytic subunits Proteins tagged for degradation with ubiquitin protein targets cap recognize and unfold protein enter core broken down to short peptides released into cytosol
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Peptides are continuously being transported from the cytosol to the ER ABC proteins: TAP1 and TAP2 form a heterodimer in ER membrane ATP-dependent peptide transporter ATP hydrolysis needed to internalize peptides into the ER Channel through which a peptide can enter ER lumen TAP1, TAP2 hydrophobic
domains (transmembrane / ER lumen) and ATP-binding domain (cytosol) dimerize four domain transporter
During synthesis MHC molecules are translocated to the ER lumen In the ER MHC molecules are in a partially folded state: MHC class 1chain must associate with 2microglobulin and then with a peptide chain binds to chaperone protein calnexin When2-microglobulin binds to chain, heterodimer dissociates from calnexin and binds to PLC
References
Murphy, K.M. (2012). Janeways Immunobiology (8th ed. pp. 8-9, & 13542). New York, NY: Garland Science Taylor & Francis Group. Creswell, P., Ackerman, A.L., Giodini, A., Peaper, D.R., & Wearsch, P.A. (2005). Mechanisms of MHC class I-restricted antigen processing and cross presentation. Immunol. Rev., 207, 145-57. Yewdell, J.W., & Bennink, J.R. (1999). Mechanisms of viral interference with MHC class I antigen processing and presentation. Aunnu. Rev. Cell Dev. Biol., 15, 579-606.