2 important immune membrane molecules 2 important immune membrane molecules ---leukocyte differentiation antigen and ---leukocyte differentiation antigen and adhesion moleculesadhesion molecules

Chapter 7Chapter 7

A.Leukocyte differentiation Ag( 白细胞分化抗原 )

B.Cluster of differentiation(CD, 分化群 )

不同谱系不同谱系 ((lineage)lineage) 白细胞在正常分化、成熟的不同白细胞在正常分化、成熟的不同阶段以及活化过程中阶段以及活化过程中 ,, 出现或消失的细胞表面标记，称为出现或消失的细胞表面标记，称为白细胞分化抗原白细胞分化抗原 ,, 多为跨膜糖蛋白。多为跨膜糖蛋白。

--- --- 应用以单克隆抗体鉴定为主的方法，将来自不同实验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化群 ((CD), CD), 以代替分化抗原以往的命名以代替分化抗原以往的命名

1.1.ConceptionConception

CD1~CD166 (CD247)

ⅠⅠ. . Leukocyte Leukocyte differentiation antigen differentiation antigen

A.CD molecules associated with reco-A.CD molecules associated with reco-gnition,adhesion and activation of T cellgnition,adhesion and activation of T cell

B.CD molecules associated with reco-B.CD molecules associated with reco-gnition,adhesion and activation of B cellgnition,adhesion and activation of B cell

2.2.Classification of CDClassification of CD

(CD3 、 CD4 、 CD8 、 CD28 、 CD2 、CD58 、 CD152 and CDL40)

(CD79a/CD79b 、 CD19/CD21/CD81 、 CD20 、 CD22 、 CD40)

(CD64/CD32/CD16 、 CD89 and CD23)

C.Fc receptor of IgC.Fc receptor of Ig

A.A.CD molecules associated with CD molecules associated with reco-gnitionreco-gnition,,adhesion and adhesion and activation of T cellactivation of T cell

②

③

④

⑤

︱MHC-Ⅰ

︱MHC-Ⅱ

︱B7

︱ CD40

︱ CD58

︱CD2 ligand

①

8 9

p67

CD3 molecules

① CD3 CD3 moleculemolecule

(CD3 分子通过盐桥与 TCR 形成 TCR-CD3 复合物 )

• • cconsist of five chain,termed onsist of five chain,termed , , , , , , and and

•• contain ITAM in the cytoplasmic regioncontain ITAM in the cytoplasmic region

•• function of CD3 function of CD3 molecule :transmit molecule :transmit activatory signalactivatory signal

ITAM

• • combine with TCR→ → TCR-CD3 complexcombine with TCR→ → TCR-CD3 complex ( 免疫受体酪氨酸活化基序 )

②② CD4 and CD4 and CD8CD8

•• functiofunctionn

•• transmembrane glycoproteintransmembrane glycoprotein••co-receptor of T cellco-receptor of T cell*CD4: first and second domains bind to nonpolymorphic region of MHC moleculesⅡ* CD8: IgV-like domain of chain binds to nonpolymorphic 3 region of MHC moleculesⅠ

•• first V-like domain of CD4 first V-like domain of CD4 ---specific receptor of HIV---specific receptor of HIV

* 介导细胞间的粘附作用 * 参与 TCR-CD3 信号传导

APC

T 细胞

③ CD28 and CD152 (CTLA-CD28 and CD152 (CTLA-4)4)

•• CD28CD28+ + cellcell ---all CD4---all CD4++ T cell and T cell and 50% CD850% CD8+ + TT cell;cell; CTLA-4CTLA-4+ + cell cell

--- activated T cell--- activated T cell

**CD28: provide an co-stimulatory signal for T cell

** CTLA-4:suppress amplification of activated T cell (bring into play negative regulation ）

5

CTLA-4CTLA-4 与与 CD28CD28 有一定有一定同源性同源性 ,, 配体均为配体均为 B7B7 家族 家族

•• binding to binding to B7-1 (CD80) and B7-1 (CD80) and B7-2 (CD86) on the surface of B7-2 (CD86) on the surface of APCAPC

④ CD2 and CD58CD2 and CD58 (or LFA-2 and LFA-3)

•• CD2 CD2 also called SRBC-Ralso called SRBC-R(( 绵羊红细胞受体绵羊红细胞受体 ))

•• ssmilar structure milar structure • • ligand of CD2---CD58 ligand of CD2---CD58 ligand of CD58---CD2ligand of CD58---CD2

5

⑤CD40L(CD154)CD40L(CD154)• • ligand of CD40ligand of CD40•• interaction of CD40L with CD40: provide interaction of CD40L with CD40: provide secondary signal for activation of B cellsecondary signal for activation of B cell

B.CD molecules associated with B.CD molecules associated with recognitionrecognition, , adhesion and activation of B celladhesion and activation of B cell

①

②

③

④

①

14

p69p69

①① CD79a/CD79bCD79a/CD79b ((alsoalso called Ig called Ig/Ig/Ig))

•• heterodimer linked by disulfide bondheterodimer linked by disulfide bond

•• contain ITAM in cytoplasmic regioncontain ITAM in cytoplasmic region

•• link with BCR→BCR complexlink with BCR→BCR complex

• • functionfunction (transmit activatory signal )

②CD40CD40 ((belong to TNFRSF)belong to TNFRSF)

•• express on mature B cell express on mature B cell

• • ligand: CD40L on T cell ligand: CD40L on T cell

③ Signalling Signalling complexcomplex••consist ofconsist of CD19, CD19, CD21, and CD81CD21, and CD81

••co-receptor of co-receptor of activation for B cellactivation for B cell

信号复合物信号复合物

(CD21---receptor of EBV; CD81---receptor of HCV )(CD21---receptor of EBV; CD81---receptor of HCV )

④CD80/CD86 CD80/CD86 (B7-1 and B7-2 of B7 families)

---V-like domain of ---V-like domain of extramembraneextramembrane region region combines with CD28/CTLA-4combines with CD28/CTLA-4

C.Fc receptor of immunoglobulinC.Fc receptor of immunoglobulin

(2)

FcR

* 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

•• IgFcIgFc 段通过与段通过与 FcRFcR 结合介导结合介导 IgIg 的生理功能或参与病理损的生理功能或参与病理损伤伤

•• 属于属于 CDCD 分子的分子的 FcFc 受体有受体有 FcFcRR 、、 FcFcR R 、 、FcFcRⅡRⅡ

p70p70

ⅡⅡ .Adhesion.Adhesion molecules molecules ( AM)( AM)1.1.ConceptionConception

AMAM 是一类介导细胞间或细胞与细胞外基是一类介导细胞间或细胞与细胞外基质质 ((ECM)ECM) 间相互接触和结合的膜表面糖蛋白间相互接触和结合的膜表面糖蛋白 ,,大部分大部分 AMAM 也属也属 CDCD 分子分子

Integrin familyIntegrin family IgSFIgSF Selectin familySelectin family

Cadherin Cadherin

2.2.ClassificationClassification 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 .

--- 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