Antigen Processing and Presentation

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Maturation and loading of MHC class I
Peptide Peptide
Peptide
Endoplasmic reticulum
B2-m Calnexin binds binds and to nascent stabilises class I chain floppy until 2-m binds MHC Tapasin, calreticulin, TAP 1 & 2 form a complex with the floppy MHC Cytoplasmic peptides are loaded onto the MHC molecule and the structure becomes compact
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endogenous antigens ： proteins that are synthesized within the cytoplasm of the cell. Examples: viral proteins, tumor antigens exogenous antigens：antigens originate outside the cell. Examples: bacteria proteins
Cells that display peptides associated with class II MHC molecules to CD4+ Th cells are called APC.
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APCs: highly specialized cells Uptake and process antigens
Ag processing and presentation
T cell response
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Since all cells expressing either class I or class II MHC molecules can present peptides to T cells, strictly speaking they all could be designated as Antigen Presenting Cells (APC). However,………………..
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The 3 types of APCs
Constitutively express a high level of MHC II and the co-stimulatory protein,B7. the most effective APC
must be activated by the process of phagocytosis before expressing class II MHC and B7.
The components of the proteasome include MECL-1, LMP2, LMP7 LMP2 & 7 encoded in the MHC
Proteasome cleaves proteins after hydrophobic and releases peptides into the cytoplasm
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Peptide antigens produced in the cytoplasm are physically separated from newly formed MHC class I
ENDOPLASMIC RETICULUM
Newly synthesized MHC class I molecules
抗原加工提呈
（Antigen Processing and Presentation） 张 勇
上海交通大学医学院免疫学教研室
T cells do not recognize native antigens
Cross-linking of surface membrane Ig
T
YYY Y Y Y Y Y
Target cell
“kiss of dead”
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上海交通大学医学院免疫学教研室
Processing and Presentation
of Exogenous Antigens
(MHC class II pathway)
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Uptake of exogenous antigens
CYTOSOL
Peptides need access to the ER in order to be loaded onto MHC class I molecules
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Transporters associated with antigen processing (TAP1 & 2)
Membrane Ig receptor mediated uptake
Y
Complement receptor mediated phagocytosis
Phagocytosis
Pinocytosis
Y
Fc receptor mediated phagocytosis
Uptake mechanisms direct antigen into intracellular vesicles for exogenous antigen processing
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2. macrophage( M)
monocyte：blood
macrophage：tissue
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3. B lymphocyte
• BCR (smIg): take up soluble antigens efficintly • Constitutively express class Ⅱ MHC • Inducible expression of B7
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The properties of various APCs
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Antigen processing and presentation antigen processing protein antigen is degraded into peptide antigen presentation association of peptide with MHC and transportation of MHC-peptide complex to the cell membrane
Constitutively express class II MHC but must be activated to produce B7.
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1. dendritic cell (DC)
discovered in 1973
Tissue –resident DC Immature DC(iDC) surface receptors recognize microbes migrate to local lymph nodes Within lymph nodes DC mature DC(mDC) present antigens to T cells in MHC molecules
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Processing and Presentation of Endogenous Antigens
(MHC class I pathway)
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Degradation in the proteasome
Cytoplasmic cellular proteins, including non-self proteins are degraded continuously by a multicatalytic protease of 28 subunits
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Target cells:
Cells that display peptides associated with class I MHC molecules to CD8+ Tc cells are referred to as target cells.
Professional antigen presenting cells (APC):
Hydrophobic transmembrane domain
Peptide
Lumen of ER
ER membrane Cytosol
Peptide Peptide
Peptide antigens from proteasome
ATP-binding cassette (ABC) domain
Transporter has preference for >8 amino acid peptides with hydrophobic C termini.
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iDC
mDC
Low levels of class II MHC and B7 Strongly internalize antigens but have no presentation ability
high levels of class II MHC and B7 Strongly present antigens but can’t uptake antigens
Express co-stimulatory molecules ( B7 )