Ag. processing.ppt

ANTIGEN
PROCESSING AND
PRESENTATION
Dr. Ahmed M. Salih
Ag. processing.ppt
Ag. processing.ppt
Ag. processing.ppt
 Professional APC
 Macrophages, dendritic cells, and B cells,
which can express MHC class II molecules.
 Other cell type capable of expressing MHC
class II molecules
eg. Endothelial cells, EC
Fibroblasts
Activated T cell
1. Binding and uptake of antigen
 depends on the physical state of the antigen and
the cell type involved.
2. Antigen processing
 MHC class I processing pathway
 MHC class II processing pathway
3. Antigen presentation
Antigen processing
1 Binding and uptake of antigen
 exogenous antigens
 Bacteria, cells and soluble proteins
 processed by APC
 endogenous antigens
 Produced within the cells, Such as viral proteins or
tumor proteins
 processed by host cell
Ag. processing.ppt
Uptake antigen by immature DC
 Pinocytosis
 Liquid or small granule
 Receptor-mediated endocytosis
 effective
 selective
 saturated
 FCR, R
 Phagocytosis
 Large molecular or microbe
 Phagocytosis
 Large solid or molecular complex, such as
bacteria, fragment of cells, etc.
 Phagecyte (mf, granulocyte)
 Pinocytosis
 Receptor-mediated pinocytosis
 Endocytosis
 Low levels of particulate or soluble antigens
 exocytosis
Uptake antigen by MPC
 nonspecifically engulfed
 BCR-mediated
Uptake antigen by B cells
2 Antigen processing
 Degradation of externally- or internally- derived
antigen into short peptide sequences
 Association of the peptide with MHC molecules
Two antigen-processing pathways
MHC class I MHC class II
Major antigen
sources
endogenous
antigen
exogenous antigen
Processing
machinery
proteasome lysosomal enzymes
Cell type where
active
all nucleated cells professional APCs
Site of antigen-
MHC binding
endoplasmic
reticulum
lysosome and
endosome
MHC utilized MHC class I MHC class II
Presents to CD8+ T cell (Tc) CD4+ T cells (Th)
MHC class I
processing pathway
MHC class I processing pathway
Antigenic protein - proteosome - peptide fragment
released into cytosol - binds to TAP protein
moves to endoplasmic reticulum(ER)
Newly synthesized Class I a chain and b2
microglobulin - move to ER calnexin binds to a
chain peptide fragment and b2m bind to a chain
release of a chain from calnexin complex moves
to Golgi apparatus glycosylation in Golgi
apparatus secretory vesicle plasma membrane
Ag. processing.ppt
Ag. processing.ppt
Ag. processing.ppt
Ag. processing.ppt
Ag. processing.ppt
proteasome
 LMP, low molecular weight polypeptide or large
multifunctional protease
 Structure:
 20S - 26S
 Function:
 Degradation of protein
Ag. processing.ppt
26S protease cmplex
20S proteasome
twin 19S cops
TAP, transporter associated with
antigen processing
 structure:
 TAP-1 and TAP-2
 function:
 transports small peptides (8-13 aa) to the ER
Molecular chaperones: calnexin,
calreticulin,tapasin
MHC class II
processing pathway
Ag. processing.ppt
 Antigenic protein - endosome/lysosome
peptide fragment
 Newly synthesized class II molecules move to
ER and associate with invariant chain protein
molecule move to Golgi apparatus move to
endosomes/lysosomes release of invariant
chain from class II molecule class II binds
antigenic peptide fragment transport to cell
surface
MHC class II processing
pathway
Endosome & lysosome
 acidic protease & lysosome enzymes
 Function
 Degrade protein into peptide fragments (10-30 aa)
invariant chain, Ii
 Function
 Promote the formation of MHC II a b dimer
 Directs the movement of newly synthesized
class II molecules into the Golgi and then the
late endocytic compartment of the cell
 Prevent the binding of antigenic peptides to
class II molecules, at least until the class II
molecule reaches the late endocytic
compartment
Ag. processing.ppt
3 Antigen presentation
 Antigen presentation
 The activation of T cells via T cell receptors, which
specifically recognize antigenic peptide in association
with either MHC class I or II molecules on the
surface of APC.
Ag. processing.ppt
Thank You
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Ag. processing.ppt

  • 5.  Professional APC  Macrophages, dendritic cells, and B cells, which can express MHC class II molecules.  Other cell type capable of expressing MHC class II molecules eg. Endothelial cells, EC Fibroblasts Activated T cell
  • 6. 1. Binding and uptake of antigen  depends on the physical state of the antigen and the cell type involved. 2. Antigen processing  MHC class I processing pathway  MHC class II processing pathway 3. Antigen presentation Antigen processing
  • 7. 1 Binding and uptake of antigen  exogenous antigens  Bacteria, cells and soluble proteins  processed by APC  endogenous antigens  Produced within the cells, Such as viral proteins or tumor proteins  processed by host cell
  • 9. Uptake antigen by immature DC  Pinocytosis  Liquid or small granule  Receptor-mediated endocytosis  effective  selective  saturated  FCR, R  Phagocytosis  Large molecular or microbe
  • 10.  Phagocytosis  Large solid or molecular complex, such as bacteria, fragment of cells, etc.  Phagecyte (mf, granulocyte)  Pinocytosis  Receptor-mediated pinocytosis  Endocytosis  Low levels of particulate or soluble antigens  exocytosis Uptake antigen by MPC
  • 11.  nonspecifically engulfed  BCR-mediated Uptake antigen by B cells
  • 12. 2 Antigen processing  Degradation of externally- or internally- derived antigen into short peptide sequences  Association of the peptide with MHC molecules
  • 13. Two antigen-processing pathways MHC class I MHC class II Major antigen sources endogenous antigen exogenous antigen Processing machinery proteasome lysosomal enzymes Cell type where active all nucleated cells professional APCs Site of antigen- MHC binding endoplasmic reticulum lysosome and endosome MHC utilized MHC class I MHC class II Presents to CD8+ T cell (Tc) CD4+ T cells (Th)
  • 15. MHC class I processing pathway Antigenic protein - proteosome - peptide fragment released into cytosol - binds to TAP protein moves to endoplasmic reticulum(ER) Newly synthesized Class I a chain and b2 microglobulin - move to ER calnexin binds to a chain peptide fragment and b2m bind to a chain release of a chain from calnexin complex moves to Golgi apparatus glycosylation in Golgi apparatus secretory vesicle plasma membrane
  • 21. proteasome  LMP, low molecular weight polypeptide or large multifunctional protease  Structure:  20S - 26S  Function:  Degradation of protein
  • 23. 26S protease cmplex 20S proteasome twin 19S cops
  • 24. TAP, transporter associated with antigen processing  structure:  TAP-1 and TAP-2  function:  transports small peptides (8-13 aa) to the ER
  • 28.  Antigenic protein - endosome/lysosome peptide fragment  Newly synthesized class II molecules move to ER and associate with invariant chain protein molecule move to Golgi apparatus move to endosomes/lysosomes release of invariant chain from class II molecule class II binds antigenic peptide fragment transport to cell surface MHC class II processing pathway
  • 29. Endosome & lysosome  acidic protease & lysosome enzymes  Function  Degrade protein into peptide fragments (10-30 aa)
  • 30. invariant chain, Ii  Function  Promote the formation of MHC II a b dimer  Directs the movement of newly synthesized class II molecules into the Golgi and then the late endocytic compartment of the cell  Prevent the binding of antigenic peptides to class II molecules, at least until the class II molecule reaches the late endocytic compartment
  • 32. 3 Antigen presentation  Antigen presentation  The activation of T cells via T cell receptors, which specifically recognize antigenic peptide in association with either MHC class I or II molecules on the surface of APC.