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Antigen-presenting cells and antigen presentation
1.Nature of antigen-presenting cells
2. Antigen processing and
presentation
Antigen Presenting Cell (APC)
Section 1 Nature of antigenpresenting cells
Antigen-presenting cells （Antigen
Presenting Cell, APC) are the
immunocytes that can uptake, process
and present antigens to lymphocytes.
Professional APC
Dendritic cells, mononuclear phagocyte
system, B cells, and APC that constitutively
express MHC II molecules
Non-professional APC
Dendritic cells
DC are the most powerful APC in vivo, which
can effectively stimulate naïve T cells to
proliferate. Yet M and B cells can only
stimulate activated or memory T cells.
Multiple hematopoietic stem cell
Lymphoid stem cell
Myeloid stem cell
Neutrophil
Myeloid DC
Monocyte
NK cell
Lymphoid DC
T cell
B cell
Macrophage
Myeloid DC
Origination of dendritic cells(DC)
Tissue distribution ：
Lymphoid DC:interdigitating DC,
marginal DC
Non-lymphoid DC: interstitial DC, LC,
gastrointestinal epithelial DC
Humoral DC: veiled cell
Blood DC
Differentiation and development of DC
precusor
immature stage （immature DC）
migratory stage
mature stage（mature DC）
Immature DC
Distribution: many solid organs and non
lymphatic epithelia
Major role: uptake and process antigen
Normally, most DC are immature DC.
Mature DC
Distribution: T lymphocyte areas in lymph node,
spleen, and Peyer’s node, blood
Characteristics: abundantly express MHC II、
MHC I、CD80、CD86、CD40、ICAM-1、HSP、
CD1a、CD11c、CD83
Major role: antigen presentation, present
peptide:MHC complex to T cells
Antigen uptaking pathways by
DC
 macropinocytosis
 receptor-mediated
endocytosis
 phagocytosis
2. Mononuclear macrophages
M ：
Origination and distribution
Bone marrow pluripotent stem
mononuclear cells-macrophages
cells-
Antigen processing and presentation of M
endocytosis or internalization：
phagocytosis
Pinocytosis
receptor-mediated endocytosis
Only those M in vigorous metabolism
have the capacity of antigen presentation.
Macrophagocytosis
mIg mediated endocytosis
Complement receptor mediated endocytosis
Pinocytosis
Fc receptor mediated endocytosis
Uptake of exogenous antigens
3 B lymphocytes
Receptor-mediated
endocytosis
Non-specific pinocytosis
Dendritic cell
macrophage
Staining of APC
B cell
Section 2 Antigen processing and
presentation
1 Antigen uptaking
DC capture antigens ：
Macropinocytosis
Receptor-mediated endocytosis
Phagocytosis
Mononuclear macrophage capture antigens:
Phagocytosis
Pinocytosis
Receptor-mediated endocytosis
B cells captureantigens:
Non-specific pinocytosis
Antigen-specific
mediated
receptor
2. Antigen processing
1、Endogenous pathway
Antigens: intracellular synthesized antigens
Presenting molecules：MHC-I
Processing region: Proteosome (polyubiquitination)
Binding region: ER
Cell surface
cytoplasm
Golgi complex
Endoplasmic reticulum
calnexin
MHC Ia chain
Degraded antigens
proteasome
Endogenous antigens
Processing and presentation of endogenous antigens
(1) Production of endogenous
antigenic peptide
Ubiquitination of endogenous
antigens
Degradation of endogenous
antigens in proteosome
Peptides containing 8-12
amino acid residues
(2) Transportation of endogenous
antigenic peptide
Endogenous antigenic peptide enter
endoplasmic reticulum:
Transporter associated with
antigen processing(TAP)
Schematic diagram of TAP structure
（3） MHC class I molecules peptide loading
Class I molecules associate with chaperon:
Bind to endogenous antigenic peptides
Enter Golgi complex to undergo
glycosylation modification
Traffick to cell surface in exocytic vesicles
and recognized by CD8+ T cells
Membrane
Antigen-MHC class 1 molecule compl
β2 microglobulin
Heavy chain of antigen-MHC class 1 molecule
Golgi complex
β2 microglobulin
Calnexin
Endogenous antigen
Proteasome
Antigenic peptide
Presentation of
endogenous antigens
2.
Presenting
pathway
of
antigens(Exogenous pathway)
Antigen: extracellular antigens
Presenting molecules: MHC-II
Processing region: endosome
Binding region: MIIC、CIIV
exogenous
Cell surface
Exogenous antigens
Fusion
Late endosome
Early endosome
Antigen degradation
Golgi complex
MHC class 2 molecule
Endoplasmic reticulum
Ii chain
Processing and presentation of exogenous antigens
Antigen processing compartment
Endosome
MHC class II、HLA-DM, and
exogenous antigenic peptide are found in
abundance.
（2）Degradation of protein antigen
Peptides containing 12-20 amino
acid residues
Endopeptidase
Exopeptidase
MHC class II molecules are transported
from ER to endosome.
Calnexin
Ia associated invariant chain(Ii chain):
Class II associated invariant chain
peptide （CLIP）
Form nonamer with ,  chain
Enter endosome through transGolgi network
Function of Ii
To prevent degradation of MHC class II molecule
during its transportation
CLIP binds to the grooves in MHC class II molecule
（4）Ii degradation in
endosome
（5）Class II molecules peptide
loading
Class II molecules peptide loading
（6）Presentation of exogenous
antigens
Exocytic vesicles
Expressed on APC
Recognized by CD4+ T cells
Antigen
Phagocytosis
Antigen
Antigenic peptide-MHC
class 2 molecule complex
internalization
B cell
Macrophage
Endosome/lysosome
Golgi complex
ER
αβIi complex
Ii chain
Antigenic peptide-MHC
class 2 molecule complex
Presentation of exogenous antigens
Comparison of endogenous and exogenous antigen-presenting pathway
Characteristics Endogenous pathway
Presenting molecule
Responding T cells
MHC-I
CD8＋ T cells
Antigen resources endogenously synthesized
exogenous pathway
MHC-II
CD4＋ T cells
exogenous uptaken
Synthesizing region
of antigen peptides
Chaperon
Presenting cells
proteosome
Calnexin, TAP, tapasin
all nucleated cells
endosome
Calnexin, Ii chain
professional APC
3. Antigen presentation
1. Basic procedure of antigen
presentation
CD8+ T
cells
Tumor cells
2.Cross presentation of antigens
by MHC molecules
（Cross priming pathway）
Master cell types, definition and
characteristics of APC
Master types of professional APC
Master the pathway and procedure of
exogenous and endogenous antigen
presentation
Familiarize antigen cross presentation
Understand the distribution and
characteristics of various kinds of
professional APC
Understand development, differentiation,
maturation and migration of DC