Transcript Cytokines and Chemokines

Chapter VII
Leukocyte differentiation antigen
and
Adhesion molecule
1. LDA，CD，CAM
2. Functional molecule and human
leukocyte differentiation antigen on
immunocyte surface
3. Clinical application of CD and
adhesion molecule as well as their
monoclonal antibody
Cell Surface Molecules
• Leukocyte differentiation
antigen(LDA) :The cell surface
markers which express or disappear
on the different leukocytes in the
different stage of differentiation and
activation.
LDA
• Expressed on leukocyte, erythroid
lineage and megakaryocyte or
thrombocyte lineage
• Other non-hematopoietic cells
• Transmembrane protein or
glycoprotein
• Some are anchored on plasma
membrane with GPI conjuction
Classification of LDA
•
•
•
•
•
•
Immunoglobulin superfamily
Cytokine receptor family
Type C lectin superfamily
Integrin family
TNF superfamily
TNF receptor superfamily
Cell Surface Molecules
• CD (cluster of differentiation) : Cell
surface molecules of leucocytes that
are distinguishable with monoclonal
antibodies as an immunologic
marker.
• HCDM（Human cell differentiation
molecules）
Cell Surface Molecules and HLDA
• Surface Molecules of Immune cells
Receptors: TCR, BCR, PRR, CKR, CR
MHC: MHCⅠⅡ
Co-stimulatory Molecules: CD28
Adhesion Molecules: integrin,selectin
一、CD molecules of T lymphocytes(p98)
1，CD3
• Consists of 5 proteins that are
designated as , , ,  and .
• Three dimers: , ,  ()
• The cytoplasmic domain contains ITAM
(immunoreceptor tyrosine-based
activation motif) YxxL/V
• Function: transduction of signals that
lead to T cell activation.
2. CD4 and CD8
 Coreceptors Involved in MHC-Restricted
T Cell Activation
 Function:CD4 and CD8 are T cell proteins
that bind to nonpolymorphic regions of
MHC molecules and transduce signals
that together with signals delivered by the
TCR complex initiate T cell activation.
 CD4:Receptor of HIV gp120
Structure of CD4
Structure of CD8
3. CD28 and CTLA-4

CD28: its ligands are B7 family molecules,
including B7-1/2 (CD80/CD86)
Function: costimulation, activation of
T cells

CTLA-4(CD152): homodimer, homologous to
CD28.
Function: inhibits T cell costimulation (the
cytoplasmic domain contains ITIM)
4、CD154（CD40L）
二、CD molecules of B lymphocytes(p92)
1,Ig/Ig (CD79a/CD79b)
• heterodimer cytoplasmic domains
contain ITAM.
Function: 1. transfers the signals that
lead to B cell activation.
2. transports the Ig
2. CD19/CD21/CD81/CD225
 CD19/CD21/CD81 interactions with
complement associated with antigen play
a role in antigen-induced B-cell activation.
 CD21=CR2, C3dR, EBV R
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4，CD40 interacts with CD40L (Th cell)
5，CD80(B7.1), CD86(B7.2)
expressed on activated B cells
6，ICAM-1, LFA-1
三、Ig Fc Receptor
Cell adhesion molecules
• CAM: A group of proteins involved
in adhesion of cell to cell or cell to
extra-cellular matrix (ECM), such as
ICAM-1, ICAM-2, ICAM-3, VCAM-1
and PECAM etc.
Cell adhesion molecules
• Cellular recognition, activation,
proliferation, differentiation, migration
• Immune response
• Inflammation
• Tumour
Cell adhesion molecules
The denomination of adhesion molecule
and CD molecule is based on different
aspects.

Adhesion molecules are classified by
adhesive function.

Most adhesion molecules possess a CD
number, however, some do not.

Categories of CAM
1. Integrin family
2. Selectin family
3. Cadherin
4. IGSF (Ig superfamily)
5. Mucin-like family
6. Others:PNAd, CD44, CD36
1, Integrin Family
1)Integrin:Mediate adhesion of cell
and extracellular matrix
2)Elementary structure: heterodimer
of ,  chain
14 kinds of  subunits, 8 kinds of 
subunits
Integrin
3)Integrin family
β1: VLA(very late appearing antigen)
β2: LFA-1(lymphocyte function
associated antigen-1)
ligand:ICAM-1,2,3
β3: gpⅡbⅢa
4)Distribution:Expressed extensively
2、Selectin Family
Selectins are carbohydrate-binding
proteins present on leukocytes,
endothelial cells, and platelets; their
principal function is to regulate the
migration of leukocytes to various
tissues
Selectin Size
L-
E-
P-
Distribution
90-110 kD Lymphocytes (high expression
select
(variati
on naive T cells, low
in
on due
expression on activated
(CD6
to
effector and memory cells)
2L)
glycosy
lation)
select
in
(CD6
2E)
select
in
(CD6
2P)
Ligand
Sulfated glycosaminoglycans on
GlyCAM-1, CD34,
MadCAM-1, others
110 kD
Endothelium activated by
cytokines (TNF, IL-1)
Sialylated Lewis X
and related
glycans (e.g., CLA1) on various
glycoproteins
140 kD
Storage granules and surface of
endothelium and platelets
Sialylated Lewis X
and related
glycans on PSGL-1
and other
glycoproteins
Functions of CAM
1. As co-receptors and co-stimulating
signal in immune cells recognition
T cell ←------ APC:
TCR
Ag-MHC molecule
CD4/CD8
MHCⅠ/Ⅱ
CD28
B7(CD80/CD86)
LFA-1
ICAM-1
2. Adhesion between leukocytes and
vascular endothelial cells in
inflammation
3. Lymphocyte homing
(1) The migration of mature lymphocytes from
primary to secondary lymphoid tissues.
(2) lymphocyte recirculation
(3) The migration of lymphocytes into the
inflammatory site.
Lymphocyte homing receptor---vascular
addressin
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Application of CD, CAM and Their
McAb
1. Investigate the mechanism of diseases
CD4 and AIDS
CD18 and LAD (Leukocyte adhesion deficiency)
2. Application in diagnosis
leukemia, AIDS (ratio of CD4/CD8 T cells)
3. Prophylactic and Therapeutic application
Graft rejection: Anti-CD3, Anti-CD25
non-Hodgkin’s lymphoma: Anti-CD20