Antigen Processing and Presentation

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? ? ? ? ? ? (Antigen Processing and Presentation)
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T cells do not recognize native antigens
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Antigens must be processed in order to be
recognized by T cells
Ag processing and presentation
T cell response
No T cell response
No T cell response
No T cell response
No 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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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.
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• 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.

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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
Constitutively express class II MHC but must be
activated to produce B7.
must be activated by the process of phagocytosis
before expressing class II MHC and 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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mDC
iDC
high levels of class II MHC and B7 Strongly
present antigens but cant uptake antigens
Low levels of class II MHC and B7 Strongly
internalize antigens but have no presentation
ability
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2. macrophage( M?)
monocyteblood macrophagetissue
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• receptors
• mannose receptor
• LPS receptor
• CR and FcRspecialized to internalize particle
  antigens
• MHC and co-stimulatory molecules
• class ? MHCinducible expressed after
  phagocytosis
• B7inducible expressed after phagocytosis

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3. B lymphocyte

• BCR (smIg) take up soluble antigens efficintly
• Constitutively express class ? 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
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endogenous antigensproteins that are synthesized
within the cytoplasm of the cell. Examples
viral proteins, tumor antigens exogenous
antigensantigens originate outside the cell.
Examples bacteria proteins
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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
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
CYTOSOL
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Transporters associated with antigen processing
(TAP1 2)
Transporter has preference for gt8 amino acid
peptides with hydrophobic C termini.
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Maturation and loading of MHC class I
B2-m binds and stabilises floppy MHC
Tapasin, calreticulin, TAP 1 2 form a complex
with the floppy MHC
Calnexin binds to nascent class I? chain until
?2-m binds
Cytoplasmic peptides are loaded onto the MHC
molecule and the structure becomes compact
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Fate of MHC class I
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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
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Processing and Presentation of Exogenous
Antigens (MHC class II pathway)
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Uptake of exogenous antigens
Membrane Ig receptor mediated uptake
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Phagocytosis
Complement receptor mediated phagocytosis
Pinocytosis
Fc receptor mediated phagocytosis
Uptake mechanisms direct antigen into
intracellular vesicles for exogenous antigen
processing
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Exogenous pathway
Protein antigens In endosome
Cathepsin B, D and L proteases are activated by
the decrease in pH
Proteases produce 1530 amino acids long peptides
from antigens
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MHC class II maturation and invariant chain
In the endoplasmic reticulum
Invariant chain stabilises MHC class II by non-
covalently binding to the immature MHC class II
molecule and forming a nonomeric complex
Need to prevent newly synthesised, unfolded self
proteins from binding to immature MHC
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Class II associated invariant chain peptide (CLIP)
(??Ii)3 complexes directed towards endosomes
by invariant chain
Cathepsin L degrades Invariant chain CLIP blocks
groove in MHC molecule
MHC Class II containing vesicles fuse with
antigen containing vesicles
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Removal of CLIP
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How can the peptide stably bind to a floppy
binding site?
Competition between large number of peptides
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HLA-DM catalyses the removal of CLIP
HLA-DM Replaces CLIP with a peptide antigen using
a catalytic mechanism
MIIC compartment
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Surface expression of MHC class II- peptide
complexes
MIIC compartment sorts peptide-MHC complexes for
surface expression or lysosomal degradation
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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.
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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.
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