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Lec 9

This document discusses antigen processing and presentation. It describes how exogenous antigens are endocytosed by antigen presenting cells, degraded into peptides, and loaded onto MHC class II molecules for presentation to CD4+ T cells. It also explains how endogenous antigens synthesized inside cells are degraded by the proteasome, transported into the ER, loaded onto MHC class I molecules, and presented to CD8+ T cells and NK cells. The document also briefly discusses how some pathogens can evade these antigen processing pathways.

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51 views16 pages

Lec 9

This document discusses antigen processing and presentation. It describes how exogenous antigens are endocytosed by antigen presenting cells, degraded into peptides, and loaded onto MHC class II molecules for presentation to CD4+ T cells. It also explains how endogenous antigens synthesized inside cells are degraded by the proteasome, transported into the ER, loaded onto MHC class I molecules, and presented to CD8+ T cells and NK cells. The document also briefly discusses how some pathogens can evade these antigen processing pathways.

Uploaded by

moh2002medicine
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPTX, PDF, TXT or read online on Scribd
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Antigen processing and

presentation
Dr.Mariam Alomari

Medical immunology M215


Lecture 8
Antigen presentation to T cells

T cells only respond to antigen presented in MHC


Processing and Presentation of Exogenous
Antigens by APC to express MHC Class II-
Peptide Complexes
• Endocytosis and phogocytosis of exogenous antigenic pathogens or
proteins in acid vesicles of APC.
• Synthesis of MHC Class II chains & assembly of MHC II in ER.
• Assembly of MHC Class II with invarient ligand (Li=CD74) that
occupies its peptide binding groove;
• Assembly of MHC Class II-CD74 leaves ER to Glolgi followed by
degradation of CD74 into CLIP (Class II Invarient Peptide).
• Fusion of MHC Class II-CLIP with acidic lysosome that contains
degraded proteins of exogenous antigens.
• Exchange of CLIP with appropriate Linear peptide epitope on
peptide binding groove & expression of the complex on APC surface
membrane for presentation to CD4+ T cell.
4
Mechanisms of Antigen and Presentation
MHCII
Processing and Presentation of Endogenous Antigens
Synthesized inside Nucleated Cells to express MHC
Class I- Peptide Complexes
• Synthesized proteins from intracellular pathogens (Endogenous
peptide antigens) broken down by proteasome ( large
cytoplasmic protein complex) and cytosolic enzymes in
cytoplasm into 8-11 a.a. long peptides.
• Selective peptides transported into E.R. by peptide transporter.
Concurrently, the infected nucleated cell has already
synthysized and assembelled full molecules of MHC Class I by
incorporating the 2 component chains.
• Association of 8-11 a.a. long peptide Ag with MHC Class I.
• MHC Class I carrying peptide Ag packaged thru Golgi and
expressed on cell surface for presentation to CD8+ T cell or NK
cells.
6
MHCI
Properties of MHC molecules and gene
Presentation of antigen to helper T cell
Presentation of antigen to Cytotoxic T cell
Evasion of Processing Pathways by Pathogens

Viral Interference:
1. a protein of herpes simplex virus (HSV) binds to TAP and inhibits peptide transport
into endoplasmic reticulum
2. Some strain of adenovirus express protein that inhibits the transcription of MHCI
(reduce the number of MHCI on cell surface)

Bacterial Interference:
Example : Mycobacterium tuberculosis inhibits phagosome –lysosome fusion
DNA Vaccination

DNA vaccines are alternatives to standard vaccination techniques and are


composed of complementary DNA (cDNA) sequences that encode protein
antigens (eg, a viral protein or tumor antigen) against which a protective
immune response is desired. “Gene guns” are used to inject DNA into cells in
subcutaneous tissues,

where the cDNA is transcribed and translated, and where some of the protein
molecules are eventually broken. Some of the peptides enter the endoplasmic
reticulum and bind to MHC class I molecules

strong and long-lived immune response to certain


antigens.

leading to presentation on class I MHC molecules


and the elicitation of a cytotoxic T-lymphocyte
response.

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