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1、 Chapter9 T lymphocytesIntroductionSurface membrane molecules on T cells and their functionsSubgroups of T cells Functions of T cells Part ISurface membrane molecules on T cells and their functionsAntigen receptor complex -recognizing antigenAccessory membrane molecules -Molecules related to the act
2、ivation of T cells (co-receptors and co-stimulators)Other surface membrane moleculesII. Antigen receptor complex of T cells: TCR and TCR complex1.TCR(1)Definition:A kind of membrane molecule on T cells that can specially bind to the antigenic peptide-MHC molecule complex(2)Types: TCR TCR (3) Structu
3、re of TCRExtracellular region: V region: V and V antigen binding site CDR1,CDR2,CDR3 C region: C and CTransmembrane region: anchoring domain positive charged Cytoplasmic regionThree dimensional structure of TCR2.TCR complex(1)Definition: A group of membrane molecule on T cells that can specially bin
4、d to the antigen and pass an activation signal into cell, consisting of TCR ( or ) and CD3(, or ) TcRCD3CD3(2)CD3 Consists of , or Important membrane molecule of T cells Contain ITAM in the cytoplasmic region Pass activatory signal into cells ITAM(Immunoreceptor tyrosine-based activation motif) : IT
5、AM is composed of 18 amino acid residues,and contains two YxxL/V consensus sequence. When TCR binds antigen specifically, the tyrosine in the consensue sequence will be phosphorylated by the receptor associated tyrosine kinases in order to transduct activatory signal. ITIM(Immunoreceptor tyrosine-ba
6、sed inhibition motif): ITIM contains I/VxYxxL consensus sequence and transducts inhibitory signal. II. Accessory membrane molecules on T cells1. CD4 and CD8: co-receptorCD4-MHC-II(2) Receptor of HIVCD8-MHC-I (3 ) CD4 and CD8 also participate in signal transduction after TCR bind antigen specifically
7、.CD4+T cell(Th)CD8+T cell(Tc)T cellReceptorPeptideMHCClass IIT cellReceptorPeptideMHCClass IAntigen PresentingCellAntigen PresentingCellCD4CD82. co-stimulatory receptor: CD28 CD28 on silent or activated T cells binds to the B7(CD80/CD86) on APC -transduct an important co-stimulatory signal to T cell
8、s CTLA-4(cytotoxic T lymphocyte antigen-4,CD152) on activated T cells binds to B7 on APC -transduct an inhibitory signal to T cells ICOS(inducible costimulator)Another co-stimulatory receptorExpressed on activated T cellsIts ligand is B7-H2Take effects after T cell activation3. CD2(LFA-2, Sheep red
9、blood cell receptor )CD2 is expressed on mature T cells, there is none on B cells.Its ligand is CD58(LFA-3) expressed on APC, RBC of human or sheep. Functions:-Mediated the formation of E-rossete.-Enhance the binding of TCR and antigenic peptide-MHC molecule complex-Participate in signal transductio
10、n of Tcell activation. 4. CD40L (CD154) CD40L on T cell binds to CD40 on B cell or other APC -Transduct a co-stimulatory signal to B cells -Promote activation of APC and T cells5. LFA-1 and ICAM-1 -Mediated adhesion between T cell and APC or target cellIII.Other surface membrane molecules 1. Mitogen
11、 receptor: -Related to lymphocyte transformation testPHA(植物血凝素), ConA(刀豆蛋白 A) -Activating T cell onlyPWM(美洲商陸) -Activating T and B cells 2. Cytokine receptor: IL-1R, IL-2R3. Class I and II MHC moleculesCD4MHC-IITCR/CD31ICAM-1B7-1B7-2LFA-1LFA-1ICAM-3LFA-3B7-1CD28CD28LFA-1ICAM-3CD22參與 Th細(xì)胞活化的膜表面分子Th細(xì)胞
12、APCCTLA-4Part II Subgroups of T cellsAccording to activatory stage of T cellsAccording to type of TCRAccording to expression of CD4 or CD8According to functions of T cell I. According to activatory stage of T cellsNave T cellActivated T cellEffecitive T cellMemory T cell Nave T cell Memory T cellsti
13、mulation of Ag no yesIL-2R(high avidity) no yesCD45 CD45RA CD45RO MHC-II molecule no yes ICAM no yesII.According to type of TCRIII. According to expression of CD4 or CD8CD4+ T cellCD8+ T cellIV. According to functions of T cellTh cell(Th1,Th2,Th3,Tr1)-CD4+Tc cell or CTL(Tc1 and Tc2)-CD8+Tr cell(CD4+
14、CD25+)Part III Functions of T cellFunctions of CD4+Th cellFunctions of CD8+ Tc cellI. Functions of CD4+Th cell Th1 IL-2,IFN- CMI Ag CD4+T cell Th0 Th2 IL-4,5,6 HI Th3 TGF- Inhibitory function Tr1 IL-10 IL-12IL-2IFN-IL-4-II. Functions of CD8+ Tc cellKill target cells specificallySecrete perforin,granzyme,granulysin -Osmotic lysis,apoptosisFas/FasL pathway -ApoptosisWhat you should know by the
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