Professional Documents
Culture Documents
Memory cells evoke a more rapid and long response on reexposure to same antigen
NTTH-HCMIU-IM-2014
RECOGNITION
HOW TO RECOGNIZE ANTIGEN?
ANTIGEN PROCESSING- WHY IS IT NECESSARY?
Because it is needed to process to be recognized
NTTH-HCMIU-IM-2014
Y
Y
Y
Y
Y
Y
Y
Cross-linking of surface
membrane Ig
YYY Y
Y Y Y Y
B B
B B BB
B B
No proliferation
No cytokine release
Y
Soluble
native Ag
Cell surface
native Ag
Soluble
peptides
of Ag
Cell surface
peptides
of Ag
ANTIGEN
PROCESSING
No T cell
response
No T cell
response
No T cell
response
No T cell
response
T cell
response
NTTH-HCMIU-IM-2014
1. Capture by antigen
specific Ig maximises
uptake of a single antigen
B
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
MHC-I association
MHC-II association
NTTH-HCMIU-IM-2014
DROPBOX
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
Professional APCs
There are 3 main types of professional antigen-presenting cells:
Dendritic cells (DCs), which have the broadest range of antigen
presentation, and are probably the most important APC. Activated DCs are
especially potent TH cell activators because, as part of their composition,
they express co-stimulatory molecules such as B7.
Macrophages, which are also CD4+ and are therefore also susceptible to
infection by HIV.
B-cells, which express (as B cell receptor) and secrete a specific antibody,
can internalize the antigen, which bind to its BCR and present it
incorporated to MHC II molecule, but are inefficient APC for most other
antigens.
Certain activated epithelial cells
NTTH-HCMIU-IM-2014
Non-professional APCs
A non-professional APC does not constitutively express the
Major Histocompatibility Complex class II (MHC class II)
proteins required for interaction with naive T cells;
These are expressed only upon stimulation of the nonprofessional APC by certain cytokines such as IFN-.
Non-professional APCs include:
Fibroblasts (skin)
Thymic epithelial cells
Thyroid epithelial cells
Glial cells (brain)
Pancreatic beta cells
Vascular endothelial cells
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
Ag processing
*MHC I interacts w/ peptides from cytosolic degradation
*MHC II interacts w/ peptides from endocytic degradation
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
Endogenous Ag processing
peptide binding to MHC-I
MHC I assembly occurs with the
aid of chaperone proteins to
promote folding (calnexin + MHC I
chain)
Tapasin + calreticulin brings TAP/
peptide close to MHC assembly
Allows MHC-I to bind to peptides
MHC I-Ag exits ER to Golgi to
plasma membrane
NTTH-HCMIU-IM-2014
Endogenous Ag processing
transport to ER
Peptides from proteolysis bind to
a transporter protein assoc w/
Ag processing (TAP)
TAP is a heterodimer which uses
ATP to help transport peptides
(8-10 aas) to lumen of ER
Usually basic aas @ COOH end
of peptide chain
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
ENDOPLASMIC RETICULUM
Newly synthesised
MHC class I molecules
CYTOSOL
Peptides need
access to the ER in
order to be loaded onto
MHC class I molecules
NTTH-HCMIU-IM-2014
Peptide
Peptide
Peptide
Endoplasmic reticulum
Calnexin binds
to nascent
class I chain
until 2-M binds
B2-M
binds and
stabilises
floppy
MHC
MHC-I Pathway
Peptide is presented
by MHC-I to CD8
cytotoxic T cell
Plasma membrane
Peptide passes
with MHC from Golgi
body to surface
rER
Peptide associates
with MHC-I complex
Proteasome
degrades
protein to
peptides
Peptide transporter
protein
moves
peptide into ER
Golgi body
NTTH-HCMIU-IM-2014
MHC-II pathway
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
in details
within ER, and chains of MHC-II combine with a protein the invariant
chain (IC, Ii, CD74)
the IC binds to MHC @peptide binding cleft + then exits the ER to Golgi
apparatus
as proteolytic activity continues, the IC is degraded to a small fragment (CLIP*)
another MHC II (HLA-DM (found in endosomes)) substitutes Ag for CLIP within
lysosome
MHC II Ag complex is transported to the PM
*CLIP = class II associated invariant chain peptide
NTTH-HCMIU-IM-2014
Removal of CLIP
HLA-DM
HLA-DR
HLA-DM
Single pocket in groove
insufficient to accommodate
a peptide
HLA-DR
Multiple pockets
in groove sufficient to
accommodate a peptide
NTTH-HCMIU-IM-2014
MIIC compartment
HLA-DM
NTTH-HCMIU-IM-2014
MHC-II Pathway
Peptide MHC-II
complex is presented
to CD4 helper T cell
Globular
protein
Endosome
Fusion of endosome
and exocytic vesicle
Endocytosis
Lysosome
Protein is processed to
peptides in endosome
or lysosome
Class II MHC
Synthesis
3 chains: , and Ii
Ii
Endoplasmic reticulum
NTTH-HCMIU-IM-2014
MHC-II Pathway
7
Globular
protein
2
b
5
4
d.
Ii
c
NTTH-HCMIU-IM-2014
Comparison of
Ag-processing pathways
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014
Summary of Ag recognition
T and B cells recognise Ag differently
Ag must be catabolised before T cells can recognise it
Ag processing generates antigenic peptides
Exogenous antigen processing takes place in lysosomes, uses invariant
chain and HLA-DM
Endogenous processing is non-lysosomal, uses proteasomes and peptide
transporters in antigen processing
The mechanism of Ag processing depends upon the compartment in which
the pathogen replicates
Endogenous and exogenous Ag processing both involve uptake,
degradation, complex formation and presentation
NTTH-HCMIU-IM-2014
EVASION of Ag presentation
NTTH-HCMIU-IM-2014
Peptide
Peptide
Endoplasmic reticulum
Sent to lysosomes
for degradation
Adenoviral
protein
retains MHC
class I in the ER
NTTH-HCMIU-IM-2014
FYI
NTTH-HCMIU-IM-2014
DC as APC
Dendritic cells = the only APC that can initiate Ag specific
response
Presumably from myeloid and lineage
Precursor DCs in blood; differentiate into immature DCs (iDC) iDC
recognized antigen with TLR and other receptors; activated
Pinocytosis/phagocytosis and cytokine production, now DC DCs can
no longer phagocytose; go to T-cell area of lymph nodes where they
present Ag to T cells
Langerhans cells are skin DC
NTTH-HCMIU-IM-2014
Figure 6-1
NTTH-HCMIU-IM-2014
Figure 6-2
NTTH-HCMIU-IM-2014
NTTH-HCMIU-IM-2014