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Chapter 7. leukocyte differentiation antigen and Adhesion molecules. 白細胞分化抗原 与粘附分子. 2 important immune membrane molecules ---leukocyte differentiation antigen and adhesion molecules. Ⅰ. Leukocyte differentiation antigen. 1. Conception.
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Chapter 7 leukocyte differentiation antigen and Adhesion molecules 白細胞分化抗原 与粘附分子 2 important immune membrane molecules ---leukocyte differentiation antigen and adhesion molecules
Ⅰ. Leukocyte differentiation antigen 1.Conception A.Leukocyte differentiation Ag(白细胞分化抗原) 不同谱系(lineage)白细胞在正常分化、成熟的不同阶段以及活化过程中,出现或消失的细胞表面标记,称为白细胞分化抗原,多为跨膜糖蛋白。 B.Cluster of differentiation(CD,分化群) --- 应用以单克隆抗体鉴定为主的方法,将来自不同实验室的单克隆抗体所识别的同一白细胞分化抗原归为一个分化群(CD), 以代替分化抗原以往的命名 CD1~CD166(CD247)
2.Classification of CD (CD3、CD4 、 CD8 、 CD28 、 CD2 、 CD58 、 CD152 and CDL40) A.CD molecules associated with reco-gnition,adhesion and activation of T cell B.CD molecules associated with reco-gnition,adhesion and activation of B cell (CD79a/CD79b 、CD19/CD21/CD81 、CD20 、CD22 、CD40) C.Fc receptor of Ig (CD64/CD32/CD16 、 CD89 and CD23)
A.CD molecules associated with reco-gnition,adhesion and activation of T cell p67 ⑤ ③ ④ ② ︱ CD2 ︱ CD58 ︱ MHC-Ⅱ ︱ MHC-Ⅰ ︱ B7 ︱ CD40 ligand ① 8 9
①CD3 molecule • consist of five chain,termed , , , and •contain ITAM in the cytoplasmic region (免疫受体酪氨酸活化基序) • combine with TCR→ → TCR-CD3 complex (CD3分子通过盐桥与TCR形成TCR-CD3复合物) •function of CD3 molecule :transmit activatory signal CD3 molecules ITAM
②CD4 and CD8 •transmembrane glycoprotein •co-receptor of T cell T细胞 *CD4: first and second domains bind to nonpolymorphic region of MHC Ⅱmolecules * CD8: IgV-like domain of chain binds to nonpolymorphic 3 region of MHCⅠmolecules APC •function *介导细胞间的粘附作用 *参与TCR-CD3信号传导 •first V-like domain of CD4 ---specific receptor of HIV
5 ③CD28 and CD152 (CTLA-4) •CD28+ cell---all CD4+ T cell and 50% CD8+ Tcell;CTLA-4+ cell --- activated T cell •binding to B7-1 (CD80) and B7-2 (CD86) on the surface of APC *CD28: provide an co-stimulatory signal for T cell*CTLA-4:suppress amplification of activated T cell (bring into play negative regulation ) CTLA-4与CD28有一定同源性,配体均为B7家族
5 ④CD2 and CD58 (or LFA-2 and LFA-3) •smilar structure • ligand of CD2---CD58 ligand of CD58---CD2 •CD2 also called SRBC-R(绵羊红细胞受体) ⑤CD40L(CD154) • ligand of CD40 •interaction of CD40L with CD40: provide secondary signal for activation of B cell
B.CD molecules associated with recognition, adhesion and activation of B cell p69 ② ④ ① ① ③ 14
①CD79a/CD79b(also called Ig/Ig) •heterodimer linked by disulfide bond •contain ITAM in cytoplasmic region •link with BCR→BCR complex • function (transmit activatory signal ) ②CD40(belong to TNFRSF) •express on mature B cell • ligand: CD40L on T cell
③Signalling complex 信号复合物 •consist ofCD19, CD21, and CD81•co-receptor of activation for B cell (CD21---receptor of EBV; CD81---receptor of HCV ) ④CD80/CD86 (B7-1 and B7-2 of B7 families) ---V-like domain of extramembrane region combines with CD28/CTLA-4
C.Fc receptor of immunoglobulin FcR p70 (2) •IgFc段通过与FcR结合介导Ig的生理功能或参与病理损伤 *介导ADCC(CD64,CD16,CD89)和吞噬作用(CD64,CD32,CD16,CD89) *B细胞表达的FcrRⅡ(胞浆区有ITIM)介导免疫抑制作用*FcRⅠ介导Ⅰ型超敏反应 ,FcR Ⅱ调节IgE的合成 •属于CD分子的Fc受体有FcR、FcR 、 FcRⅡ
AM是一类介导细胞间或细胞与细胞外基质(ECM)间相互接触和结合的膜表面糖蛋白,大部分AM也属CD分子 Ⅱ.Adhesionmolecules ( AM) 2.Classification 介导细胞与细胞外基质(ECM)/细胞间的粘附作用,使细胞附着形成整体而得名. Integrin family IgSF Selectin family Cadherin 1.Conception ---介导T-APC/靶细胞、T-B细胞间相互识别与作用 ---参与炎症发生、淋巴细胞归巢、凝血和肿 瘤转移的AM. ---介导同型粘附作用