Antigen Processing and Presentation
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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
上海交通大学医学院免疫学教研室
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
Proliferation and antibody production
B
B B B B BB B B
Y
Y
Y
Y Y Y Y Y Y
T
No proliferation
上海交通大学医学院免疫学教研室
Antigens must be processed in order to be recognized by T cells
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
上海交通大学医学院免疫学教研室
2. macrophage( M)
monocyte：blood
macrophage：tissue
上海交通大学医学院免疫学教研室
3. B lymphocyte
• BCR (smIg): take up soluble antigens efficintly • Constitutively express class Ⅱ MHC • Inducible expression of B7
CYTOSOL
Peptides need access to the ER in order to be loaded onto MHC class I molecules
上海交通大学医学院免疫学教研室
Transporters associated with antigen processing (TAP1 & 2)
Baidu Nhomakorabea
native Ag
Cell surface native Ag
Soluble peptides of Ag
No T cell response
No T cell response
No T cell response
Y
No T cell response
T
Cell surface peptides of Ag presented by cells that express MHC antigens Cell surface peptides of Ag
上海交通大学医学院免疫学教研室
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.
Constitutively express class II MHC but must be activated to produce B7.
上海交通大学医学院免疫学教研室
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
上海交通大学医学院免疫学教研室
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):
Express co-stimulatory molecules ( B7 )
Express class II MHC molecules Present antigenic peptide to CD4+ T-cell
the main APCs are: dendritic cells, macrophages and B cells.
Ag processing and presentation
T cell response
上海交通大学医学院免疫学教研室
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,………………..
上海交通大学医学院免疫学教研室
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.
上海交通大学医学院免疫学教研室
APCs: highly specialized cells Uptake and process antigens
上海交通大学医学院免疫学教研室
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
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
上海交通大学医学院免疫学教研室
Exogenous pathway
Cell surface Uptake
Protein antigens In endosome Endosomes
Increase in acidity To lysosomes
Cathepsin B, D and L proteases are activated by the decrease in pH Proteases produce 15~30 amino acids long peptides from antigens
上海交通大学医学院免疫学教研室
The properties of various APCs
上海交通大学医学院免疫学教研室
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
上海交通大学医学院免疫学教研室
Processing and Presentation of Endogenous Antigens
(MHC class I pathway)
上海交通大学医学院免疫学教研室
Degradation in the proteasome
Cytoplasmic cellular proteins, including non-self proteins are degraded continuously by a multicatalytic protease of 28 subunits
上海交通大学医学院免疫学教研室
Fate of MHC class I
Exported to the cell surface
Sent to lysosomes for degradation
上海交通大学医学院免疫学教研室
The presentation of Class I MHC/ peptide by a target cell to a CD8+ Tc cell results in the proliferation and subsequent differentiation of a Tc into a killer/effector cell. The Tc can then participate in TARGET CELL KILLING.
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.
Target cell
“kiss of dead”
上海交通大学医学院免疫学教研室
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)
上海交通大学医学院免疫学教研室
Uptake of exogenous antigens
上海交通大学医学院免疫学教研室
Peptide antigens produced in the cytoplasm are physically separated from newly formed MHC class I
ENDOPLASMIC RETICULUM
Newly synthesized MHC class I molecules
（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
上海交通大学医学院免疫学教研室
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
Proliferation and antibody production
B
B B B B BB B B
Y
Y
Y
Y Y Y Y Y Y
T
No proliferation
上海交通大学医学院免疫学教研室
Antigens must be processed in order to be recognized by T cells
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
上海交通大学医学院免疫学教研室
2. macrophage( M)
monocyte：blood
macrophage：tissue
上海交通大学医学院免疫学教研室
3. B lymphocyte
• BCR (smIg): take up soluble antigens efficintly • Constitutively express class Ⅱ MHC • Inducible expression of B7
CYTOSOL
Peptides need access to the ER in order to be loaded onto MHC class I molecules
上海交通大学医学院免疫学教研室
Transporters associated with antigen processing (TAP1 & 2)
Baidu Nhomakorabea
native Ag
Cell surface native Ag
Soluble peptides of Ag
No T cell response
No T cell response
No T cell response
Y
No T cell response
T
Cell surface peptides of Ag presented by cells that express MHC antigens Cell surface peptides of Ag
上海交通大学医学院免疫学教研室
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.
Constitutively express class II MHC but must be activated to produce B7.
上海交通大学医学院免疫学教研室
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
上海交通大学医学院免疫学教研室
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):
Express co-stimulatory molecules ( B7 )
Express class II MHC molecules Present antigenic peptide to CD4+ T-cell
the main APCs are: dendritic cells, macrophages and B cells.
Ag processing and presentation
T cell response
上海交通大学医学院免疫学教研室
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,………………..
上海交通大学医学院免疫学教研室
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.
上海交通大学医学院免疫学教研室
APCs: highly specialized cells Uptake and process antigens
上海交通大学医学院免疫学教研室
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
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
上海交通大学医学院免疫学教研室
Exogenous pathway
Cell surface Uptake
Protein antigens In endosome Endosomes
Increase in acidity To lysosomes
Cathepsin B, D and L proteases are activated by the decrease in pH Proteases produce 15~30 amino acids long peptides from antigens
上海交通大学医学院免疫学教研室
The properties of various APCs
上海交通大学医学院免疫学教研室
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
上海交通大学医学院免疫学教研室
Processing and Presentation of Endogenous Antigens
(MHC class I pathway)
上海交通大学医学院免疫学教研室
Degradation in the proteasome
Cytoplasmic cellular proteins, including non-self proteins are degraded continuously by a multicatalytic protease of 28 subunits
上海交通大学医学院免疫学教研室
Fate of MHC class I
Exported to the cell surface
Sent to lysosomes for degradation
上海交通大学医学院免疫学教研室
The presentation of Class I MHC/ peptide by a target cell to a CD8+ Tc cell results in the proliferation and subsequent differentiation of a Tc into a killer/effector cell. The Tc can then participate in TARGET CELL KILLING.
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.
Target cell
“kiss of dead”
上海交通大学医学院免疫学教研室
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)
上海交通大学医学院免疫学教研室
Uptake of exogenous antigens
上海交通大学医学院免疫学教研室
Peptide antigens produced in the cytoplasm are physically separated from newly formed MHC class I
ENDOPLASMIC RETICULUM
Newly synthesized MHC class I molecules