Chapter 7 Leukocyte differentiation antigen and cell adhesion molecules Cell membrane molecules: Antigen, receptor, others Cell surface marker

1. Leukocyte differentiation antigen

LDA family or superfamily a.IgSF b.Cytokine R F c.C Lectin SF( 凝集素） d.Integrin F （整合素） e.TNFSF f.TNFRSF

2. CD –cluster of differentation ： LDA was determined by different mAb that coming from different lab.

CD1—CD166 B cell, T cell, NK cell, Narrow line, Platelet, Adhesion molecules, Endothelial cell, Cytokine R and no lineage (see Appendix)

CD molecules （一）、 CD are associated with recognition,adhesion,activation of T cell 1.TCR-CD3 a. CD3 is a complex of five invariant polypeptide chains that associate to form three dimers( 二聚物） : a heterodimer （杂二聚体） of gamma and epsilon chains(γε), a heterodimer of delta and epsilon chains(δε), and a homodimer of two zeta chain(ζζ) or a heterodimer of zeta and eta chains(ζη)(Fig).

b. The zeta and eta chains, which are encoded by same gene, differ in their carboxyle （羧基） -terminal ends because of differences in RNA splicing of the primary transcript. About 90% of the CD3 complex examined to date incorporate the (ζζ) homodimer; the remained have the (ζη) heterodimer.

c. The γ,δ and ε chains of CD3 are member of the immunoglobulin superfamily, each containing an immunoglobulin-like extracellular domain followed by a transmember region and a cytoplasmic domain of more than 40 amino acids.

d.The ζ and η chains have a distinctly different structure: both have a very short external region of only 9 amino acids, a transmemberane region, and a long cytoplasmic tail contain 113 amino acids in ζ and 155 amino acids in η.

The transmembrane region of all the CD3 polypeptide chains contains a negatively charged aspartic acid( 天冬 氨酸） residue.These negatively charged groups enable the CD3 complex to interact with one or two positively charged amino acids in the transmembrane region of each TCR chain.

.e.The cytoplasmic tail of the CD3 chains contain a motif called immunoreceptor tyrosine-based activation motif(ITAM). This motif is found in a number of other receptors. The ITAM sites have been shown to interact with tyrosine kinases （激酶） and to play an important role in signal transduction. In CD3, the γ,δ, and ε chains contain a signal copy of ITAM, whereas the ζ and η chains contains three copies.

2. CD4 and CD8 a. T cell can be subdivided into two populations according to their expression of CD4 or CD8 memberane molecules. b. CD4 + T cell recognize antigen that is combined with class II MHC molecules and function largely as helper cells. c. CD8 + T cells recognize antigen that is combined with class I MHC molecules. They function largely as cytotoxic cells.

d. CD4 is a 55-Kda monomeric membrane glycoprotein that contains four extracellular immunoglobulin- like domains(D1-D4), a hydrophobic （疏水） transmembrane region, and a long cytoplasmic tail contain three serine （丝 aa) residues, which can be phosphorylated.

e. CD8 generally takes the form of a disulfide( 二硫键） -linked αβ heterodimer or an α α homodimer.Both the α and β chains of CD8 are small glycoprotein of approximately kDa. Each chain consists of a single extracellular Ig-like domain, a hydrophobic transmembrane region, and a cytoplasmic tail containing residues, several of which can be phosphorylated.

f. The extracellular domain of CD4 and CD8 bind to the membrane- proximal domain of MHC molecules on antigen-presenting cells(APC) or target cell: CD4 binds to the β2 domain of class II MHC molecules.

Model of the external domains of CD4(orange), T-cell receptor(blue),and class IIMHC molecule(green)showing their orientation to each other.The top of the CD4 and TCR models in this figure would be anchored in the T cell membrane; the bottom of the class II MHC molecule would be anchored in membrane of an antigen-presenting cell. Interaction between CD4 and β2 domain in the class II molecule is mediated by the residues in red The antigenic peptide is pink.

Ribbon diagram showing three dimensional structure of an HLA-A2 MHC class I molecule bound to a CD8 αα homodimer. The HLA-A2 heavy chain is shown in green,β2- microglobulin in gold, the CD8 α1 in red, the CD8 α2 in blue, and the bound peptide in white. A flexible loop the α3 domain is in contact with the two CD8 subunits. In this model, the right side of CD8 would be anchored in the T- cell membrane, and the lower left end of the class I MHC molecule anchored to surface of target cell.

3.CD2 a. CD2 is called lymphocyte function associated antigen 2, LFA-2(T11, E-rosette receptor, CD58-binding adhesion molecule). b. MW: c. Leukocyte expression: DC, B cell, Langerhans cells, some thymocytes. d. Function: Display of non-peptide and glycolipid （糖脂类） antigens for T-cell response.

4.CD58 a.Lymphocyte function associated antigen 3,LFA-3 b. MW: 5-70 Kda c. Expression: Many hematopoietic ( 造血的） and non-hematopoitic cell types. d. Function: Adhesion between killer T cells and target cells, antigen-presenting cells and T cells, or thymocytes and thymic epithelial cells.

5. CD28 a.MW: 90KDa b. Expression: Mature CD3 + thymocytes, most peripheral T cells, Plasma cells, CD4 + and 50% CD8 +. c. Function: Co-stimulation of T cell proliferation and cytokine production upon binding CD80(B7-1) and CD86(B7- 2)

T H- cell activation requires a co- stimulatory signal provided by antigen- presenting cells. Interaction of B7 family members on APCs with CD28 delivers the co- stimulatory signal. Engagement of the closely related CTLA- 4 molecule with B7 produces an inhibitory signal. All of these molecules contain at least one Ig-like domain and thus belong to Ig superfamily.

6. CTLA-4 a.Cytotoxic T lymphocyte associated antigen-4, CD152. b.Signaling through CD28 delivers a positives co-stimulatory signal to the T cell, but signal through CTLA-4 is inhibitory and down-regulates the activation of T cells.

7. CD40L

( 二） CD are associated with recognition, adhesion, activation of B cell CD79α, CD79β, CD19, CD21, CD81, CD80 and CD40

1.CD79α(mb-1/Igα)/CD79β(B29/Igβ) Component of B-cell antigen receptor analogous to CD3, required for cell-surface expression and signal transduction

CD79α(mb-1/Igα)/CD79β(B29/Igβ)

2. CD19 Part of B-cell coreceptor with CD21 and CD81; a critical signal transduction molecule that regulates B-cell development, activation, and differentiation. Expression: Follicular DC, B cells from earliest recognizable B lineage cells during development to B-cell blasts but lost on maturation to plasma cells.

3. CD21(C3dR,CR2,EBV-R) Expression: B cells, follicularDC, It’s a important marker of B cells.

4. CD80/CD86(B7-1,B7-2

5.CD40