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MECHANISMS OF ANTIGEN PROCESSING FOR CLASS I MHC PRESENTATION

By: Shelby Olesovsky and Muhammad Bin Aftab Syed

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

of peptide by MHC molecule at cell surface

MHC I Molecule CD8 T-cells MHC II Mlecule CD4 T-cells


From Janeways Immunobiology(Murphy, 2012)

Basic Overview

From Janeways Immunobiology(Murphy,

Generating the Peptide

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

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Proteaso me.html

Peptide Entry into ER

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

From Janeways Immunobiology(Murphy,

Generating MHC Class I

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

Putting it All Together

From Janeways Immunobiology(Murphy,

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.

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