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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
Y
Y
Y
Y
Y
Y
Y
Cross-linking of
surface membrane Ig
YYY Y
Y Y Y Y
B
B B
B B BB
B B
Proliferation and
antibody production
T
T
No proliferation
上海交通大学医学院免疫学教研室
Y
Y
Antigens must be processed in order
to be recognized by T cells
T
Y
native Ag
Cell surface
native Ag
Soluble
peptides
of Ag
Cell surface peptides of
Ag presented by cells that
express MHC antigens
Cell surface
peptides
of Ag
Ag processing
and presentation
No T cell
response
No T cell
response
No T cell
response
No T cell
response
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
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):
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
 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.
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
iDC
mDC
Low levels of class II
MHC and B7
high levels of class II
MHC and B7
Strongly internalize
antigens but have no
presentation ability
Strongly present
antigens but can’t
uptake antigens
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
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
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
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
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
Peptide antigens produced in the cytoplasm are
physically separated from newly formed MHC class I
ENDOPLASMIC RETICULUM
Newly synthesized
MHC class I molecules
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)
Hydrophobic
transmembrane
domain
Lumen of ER
Peptide
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.
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
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.
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
Membrane Ig
receptor mediated
uptake
Y
Phagocytosis
Complement receptor
mediated 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
MHC class II maturation and invariant chain
In the endoplasmic reticulum
Invariant chain stabilises MHC class
Need to prevent newly
II by non- covalently binding to the
synthesised, unfolded
self proteins from binding immature MHC class II molecule and
forming a nonomeric complex
to immature MHC
上海交通大学医学院免疫学教研室
Class II associated invariant chain peptide (CLIP)
Cell surface
Uptake
(Ii)3 complexes
directed towards
endosomes by
invariant chain
Endosomes
Cathepsin L degrades
Invariant chain
CLIP blocks groove in MHC
molecule
MHC Class II
containing vesicles
fuse with antigen
containing vesicles
上海交通大学医学院免疫学教研室
Removal of CLIP
?
How can the peptide stably bind to a floppy binding site?
Competition between large number of peptides
上海交通大学医学院免疫学教研室
HLA-DM catalyses the removal of CLIP
HLA-DM
Replaces CLIP with a
peptide antigen using a
catalytic mechanism
HLA-DM
MIIC compartment
Sequence in cytoplasmic
tail retains HLA-DM in
endosomes
上海交通大学医学院免疫学教研室
Surface expression of MHC class IIpeptide complexes
Exported to the cell surface (t1/2 = 50hr)
Sent to lysosomes for degradation
MIIC compartment sorts peptide-MHC complexes for surface expression or
lysosomal degradation
上海交通大学医学院免疫学教研室
The result of Class II MHC/peptide by an APC
to a CD4+ Th cell is: ACTIVATION and
PROLIFERATION of the Th cell and then
“help” other immuno-cells to activate.
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
Separate antigen-presenting
pathways are utilized for
endogenous (green) and
exogenous (red) antigens.
The mode of antigen entry
into cells and the site of
antigen processing
determine whether antigenic
peptides associate with class
I MHC molecules in the
rough endoplasmic reticulum
or with class II molecules in
endocytic compartments.
上海交通大学医学院免疫学教研室
内源性和外源性抗原加工途径特点比较
特点
内源性抗原加工途径 外源性抗原加工途径
提呈抗原肽的 MHC 分子 I 类分子
II 类分子
应答的 T 细胞
CD8+ T 细胞
CD4+ T 细胞
抗原来源
内源性
外源性
抗原肽产生部位
胞内蛋白酶体
内体、溶酶体
MHC 荷肽部位
内质网腔
CIIV 或 MIIC
伴随蛋白
钙联素，TAP，tapasin 钙联素，Ii 链
提呈细胞
所有有核细胞
专职 APC
上海交通大学医学院免疫学教研室
本章要求：
1.掌握APC的概念、种类及生物学功能。
2.掌握内源性和外源性抗原加工提呈的过
程。
3.掌握下列常用名词：
抗原加工提呈、APC、内源性抗原、外源性抗原
上海交通大学医学院免疫学教研室