Atigen Capture and

Presentation to Lymphocytes

Kusworini Handono. Wisnu Barlianto, Singgih

Wahono
Faculty of Medicine, Brawijaya University
Malang
 Antigen Recognized by T lymphocytes

• The majority of T lymphocytes recognized peptide

antigen that are bound to and displayed by the MHC
molecules on APCs or target cells (MHC restriction)
• The specialized cells that capture microbial antigen
and display them for recognition by T lymphocytes
are called APC (dendrit, macrophage and B cells)
• APC also express second signals for T cell activation
Function of Dendritic Cell as APC
 Antigen Recognized by B Lymphocytes

• B lymphocytes used membrane-bound antibodies to

recognize Ag (protein, polysacharides, lipids, small
chemical) in the native conformation
• B cell recognize to different Ag are classified as T-
dependent (for protein Ag) or T-indipendent (for
non protein Ag)
• FDC used their Fc receptor to bind Ag to activated
B cells
• B cell differentiate in response to Ag and the other
signals into cells that secrete Ab
Capture of Protein Antigen by APC
Molecular interaction that mediate naïve
T lymphocyte activation by antigen
presenting cells (APC)
CD 2
CD11a/ T LYMPHOCYTE
CD18 CD4/ CD3/ CD154
TCR CTLA-4
CD8 CD 28

CD58
CD80/ CD40
peptide/ CD86
MHC
CD54
ANTIGEN-PRESENTING
CELL
Th2 effector functions

Mechanisms in Rheumatology ©2001

Th1 effector functions

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The Structure and Function of MHC
molecules
 The Major Histocompatibility Complex
(MHC) molecules
• Membrane protein on APCs that display peptide antigens
for recognition by T lymphocytes
• Human MHC molecules are called Human Leucocyte
Antigens (HLA)
• There are 2 types : Class I and Class II MHC molecules
• The genes encoding these molecules are MHC Region of
highly polymorphic genes on 6p21 chromosome
• MHC genes are codominantly expressed
• The MHC locus in human is designated Human Leucocyte
Antigen / HLA locus
 Chromosome 6
HLA
Centromer DP DQ DR B C A

ClassII ClassII Class I

I
 Genetic organization of the HLA

• The HLA region, ± 4.000 kb, on the 6p21.3, is divided into

class I, II and III regions
• The class I region encoded : HLA-A, B and C molecules
(classical molecules) and HLA-E, F,G, H, J (non classical
molecules)
• The class II region encoded : HLA-DR, DQ and DP
molecules (classical molecules) and HLA-DM and DO (non
classical molecules).
• The class III region include : C2, C4, properdine factor B,
TNF-α, TNF-β, HSP70, 21-hydroxylase.
 CLASS I HLA MOLECULES

• Contain two separate polypeptide chain :  chain 44 kD and 

chain 12 kD
• The  chain is divided into three region : an extracellular,
transmembrane and cytoplasmic region
• The extracellular region has been subdivided into 1, 2, and 3
domain
• The  chain,  2 microglobulin, encoded by a gene outside the
MHC, on chromosome 15
• Distribution : all nucleated cells of the body
• The principal function : to bind and present of intracellular
antigen to specific CD8 lymphocytes
 CLASS II HLA MOLECULES

• Composed of two non-covalently associated polypeptide

chains :  chain 34 kD and  chain 32 kD
• Both polypeptide chains are divided into three regions : an
extracellular, transmembrane and cytoplasmic region
• The extracellular region of both the  and  chains have
been subdivided into two domains, 1, 2 and 1, 2
• Distribution : Dendritics, B lymphocytes, macrophages
and a few other cell types
• The principal function : to bind and present of
extracellular antigen to specific CD4 lymphocytes
Tujuan pembelajaran

• Memahami kepentingan mol MHC dalam

sistem imun
• Memahami struktur dan klas molekul MHC
• Mengetahui kompleks gen yang menyandi
mol MHC
• Memahami jalur prosesing dan presentasi Ag
oleh mol MHC
• Mengetahui faktor yang menghambat
prosesing dan presentasi Ag
Antigen Processing and
Presentation
 Endocytosis of extracellular antigen

Plasma Class II  + peptides

membran

endosome

endosome
Golgi
Class II
Loading compartment

Class II 
ER + CLIP
calnexin DM
70K

 +  + free
Cytosolic antigen lysosome
Invariant chain trimer
 Macropinocytosis of
Plasma membrane
Extracellular antigen

Golgi

(degradation)

TAP
re
cy

Rough ER
cli
ng

2m Cytosolic
antigen
calnexin

proteasome
Class I 
 The antigen-processing pathways
Endocytic pathway Cytosolic pathway
Major antigen source Endocytosed extracellular Cytosolic protein of host or
proteins (host & foreign) intracellular pathogens
Membrane protein (host & (viral, bacterial, parasitic)
foreign) Signal peptides (host &
foreign)
Processing machinery Lysosomal enzymes Proteasomes

Cell types where active Profesional APCs All nucleated cells

Site of antigen – MHC Endocytic vesicles, Rough endoplasmic

binding prelysosomes reticulum
MHC utilized Class II Class I

Presents to CD4 (helper) T cells CD8 (cytotoxic) T cells

Immune Responses : The Role of MHC molecules
 Control of Ag processing and presentation

• IFN : increase expression of class I mol, TAP, LMP and

class II mol
• Some infectious pathogen actively subvert these process
Herpes simplex produce protein that inactivate the TAP
AdenoVi and CytomegaloVi encode protein that inhibit
expression class I mol
 Summary
• Microba and Microbial Ag that are enter the body through epithelia are
capture by APC and transported to regional lymph node.
• Protein that are ingested by APC from the extracelluler are
proteolytically degraded within the vesicles of the APC and bind to the
clefts of newly synthesized class II MHC molecules and than are
recognized by CD4 helper T cell
• Protein that are produce by microbes living in the cytoplasm of infected
cells or enter the cytoplasm from phagocytosed microbes are degraded by
cytosolic proteases and bind to the cleft of newly synthesized class I MHC
molecules and are recognized by CD8 cytolytic T cell

•
 Summary

• Microbes activated APCs to express membrane

protein (called costimulator) and to secrete
cytokines that provide signals that function in
concert with antigen to stimulate specific T cells
• B lymphocytes recognized protein as well as non
protein antigens evens in their native
conformations
• Follicular dendritic cells displys antigens to
germinal center B cells and select the high-affinity
B cells during humoral immune responses
Clonal expansion and differentiation of activated B cells

Mechanisms in Rheumatology ©2001