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

Immunoglobulin superfamily Cytokine receptor family Type C lectin superfamily Integrin family TNF superfamily TNF receptor superfamily Classification of LDA

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: MHC ⅠⅡ 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

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. Cell adhesion molecules

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: gp Ⅱ b Ⅲ a 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

SelectinSizeDistributionLigand L- select in (CD6 2L) kD (variati on due to glycosy lation) Lymphocytes (high expression on naive T cells, low expression on activated effector and memory cells) Sulfated glycosamino- glycans on GlyCAM-1, CD34, MadCAM-1, others E- select in (CD6 2E) 110 kDEndothelium activated by cytokines (TNF, IL-1) Sialylated Lewis X and related glycans (e.g., CLA- 1) on various glycoproteins P- select in (CD6 2P) 140 kDStorage 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 MHC Ⅰ / 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