Selectin family

Cluster of Differentiation, CD
Tel:8462530; 8462468(lab)
E-mail: [email protected]
Institute of Immunolgy, weifang Medical University
Contents
• Human leukocyte differentiation antigen
(LDA).
• CD molecules
• Adhesion molecule.
• Clinical application of CD molecule .
Section 1 Functional molecule on immunocyte surface
and human leukocyte differentiation antigen
Electronic microscope image of human T lymphocyte
Functional molecule on immunocyte surface
Human Leukocyte Differentiation Antigen
(LDA)
• LDA refer to molecules on cell surface in the
differentiation into different lineages, different
stages and activation in blood cells.
Different differentiation and develop stage
Cell activation process
L-selectin
Rest
T cell
Activated
T cell
VLA-4
Classification of LDA
• Immunoglobulin superfamily.
• Cytokine receptor family.
• Type C lectin superfamily.
• Integrin family.
• TNF superfamily.
• TNF receptor superfamily.
Cluster of Differentiation: CD
• CD: Identified mainly by monoclonal antibody
(mAb). One LDA which is recognized by mAb from
different labs and whose coding gene and
expression profile have been identified, can be
designated CD.
Cluster of Differentiation: CD
• CD1-CD363
• Web site : http://www.hlda8.org
Uses of CD moleculers
• We can use one or two CD moleculers to
classified the lymphocyte precisely.
• Based on: some CD moleculer is specific to the
cells but some isn’t specific.
Section2 Cell adhesion molecules:CAM
• Adhesion molecules: mediate the binding
of one cell to other cells or to extracellular
matrix proteins.
Adhesion molecules: mediate the binding of one cell to
other cells or to extracellular matrix proteins.
Relationship between CD and CAM
• They are all the curface molecular .
• The denomination of CAM and CD is based on
different aspects.
• Adhesion molecules are classified by adhesive
function.
• Most adhesion molecules possess a CD number,
however, some do not.
Classifications: Based on structural features
• Immnoglobulin
superfamily.
• Cadherins family.
• Selectin family.
• Integrin family.
1 Immunoglobulin-like adhesion molecules
• Include a large group of molecules that are
generated from a smaller number of genes by
alternative RNA splicing.
• The best-studied members of this group are the
neural cell adhesion molecules (N-CAMs) which are
expressed predominantly in nervous tissue and the
intercellular cell adhesion molecules (ICAMs).
Neural cell adhesion molecules (N-CAMs)
• N-CAM has been found in
many different forms.
Differing amounts of
glycosylation, especially
amounts of sialic acid can alter
the adhesivity of the molecule.
• Alternative splicing of the
primary RNA transcript leads
to the production of different
forms. The following diagram
shows four forms of N-CAM.
2 Calcium dependent adhesion molecules
(Cadherins)
• A family of Ca2+-
dependent CAMs.
• Ca2+ causes
dimerization.
• Cadherins cause
adhesion via binding to
other cadherins in a
calcium-dependent
manner.
Cadherins
• Interaction with other cadherins.
• Used in organ formation
• Primarily link epithelial and muscle cells to their
neighbors.
• Play critical role during cell development.
• E-cadherins hold epithelial cells .
• N-cadherins expressed in nervous system are
responsible for the specificity of neuronal
connections.
Cadherins
Without cadherins
With cadherins
Human embryo undergoes compaction with cadherins
3 Selectin family
• Selectins are involved in cell extravasation.
• Inflammatory signals activate endothelial cells
making P-Selectin.
• P-Selectin on the surface of endothelial cells
binds a specific carbohydrate ligand on
leukocytes.
• The leukocytes attach to the endothelial wall
and roll slowly on it.
3 Selectin family
• Selectins are expressed primarily on leukocytes
and endothelial cells, is very important in many
host defense mechanisms .
• Selectins mediate interactions between leukocytes
and endothelial cells, promotes rolling of the
leukocytes along the endothelium and allows the
leukocytes to be stopped in place.
Selectin family
Molecule
L-selectin
(CD62L)
E-selectin
(CD62e)
P-selectin
(CD62P)
Ligands
GlyCAM-1 ; CD34
Distribution
Leukocytes
Cutaneous lymphocyteassociated antigen
P-selectin glycoprotein ligand1
Endothelial
cells
Endothelial
cells
Platelets
Adhesion molecules involved in leukocyte
emigration from vessels during inflammation
Rolling
L-Selectin
P-Selectin
E-Selectin
Stopping
Integrins
ICAM-1
VCAM-1
Aggregation & Shape
Change
CD11b
CD11a
P-Selectin
Migration through vessel
wall
Integrins
ICAM-1
VCAM-1
4 Integrin family
• Integrins are a diverse and large group of glycoproteins.
• The two subunits, alpha and beta, both participate in binding.
• Integrins participate in cell-cell adhesion and cells - extracellular
matrix such as fibronectin.
4 Integrin family
• Integrins facilitate "communication" between the cytoskeleton
and extracellular matrix. Interactions of integrins with the
extracellular matrix have profound effects on cell function.
• Integrins exist in "active" and "inactive" states. a group of
integrins responsible for binding of white blood cells to
endothelium are normally inactive, allowing the blood cells to
circulate freely, but become activated in response to
inflammatory mediators, resulting in the white cells being
"pulled" from blood into inflammed tissues.
βIntegrin family
Section 3 Function of Adhesion Molecule
• Co-receptor and co-stimulation signal in the
recognition of immunocyte.
• Adhesion of leukocyte and vascular endothelial cell
during the inflammation.
• Homing of Lymphocyte.
Co-receptor and co-stimulation signal in the
recognition of immunocyte
Adhesion of leukocyte and vascular endothelial cell
during the inflammation
Adhesion of leukocyte and vascular endothelial cell
during the inflammation
Homing of Lymphocyte
Section 4 Clinical Application of CD and Adhesion
Molecule as well as Their Monoclonal Antibody
• Elucidate pathogenesis.
• Application in diagnosis.
• Application in disease prevention and
treatment.
Requisition
• Master the concept of LDA, CD and adhesion
molecule.
• Master CD molecules related to T/B cell.
• Comprehend classification and functions of
adhesion molecules.
• Comprehend clinical applications of CD molecule
and adhesion molecule .