Chapter 12 Antigen receptors and accessory molecules of lymphocytes

Contents  Part Ⅰ T cell receptor complex  Part Ⅱ T cell accessory molecules  Part Ⅲ B cell antigen receptor and B cell receptor complex  Part Ⅳ B cell accessory molecules  Part Ⅴ T cell subpopulations and B cell subpopulations

Part Ⅰ T cell receptor complex  Antigen receptor complex------recognizing antigen

TCR and TCR complex

1. TCR (1)Definition: A kind of membrane molecules on T cells that can specially bind to the antigenic peptide-MHC molecule complex (2)Types ： αβTCR γδTCR

(3) Structure of TCR  Extracellular region: V region: V  and V  V region: V  and V  antigen binding site antigen binding site CDR1,CDR2,CDR3 CDR1,CDR2,CDR3CDR1,CDR2,CDR3 C region: C  and C  C region: C  and C   Transmembrane region: anchoring domain anchoring domain positive charge positive charge  Cytoplasmic region: can ’ t transduce signal can ’ t transduce signal （ 3~12aa ） + +

CDR1 CDR3CDR2

Three dimensional structure of TCR

2. TCR complex (1)Definition: A group of membrane molecules on T cells that can specially bind to the antigen and pass activation signal into T cells, consisting of TCR (  or  ), CD3( ,  ) and  chain.         TCR    CD3

(2) CD3 and  chain  Consists of , ,  or η  Important membrane molecules of T cells  Pass activation signal into T cells  Contain ITAM in the cytoplasmic region

ITAM (Immunoreceptor tyrosine- based activation motif) : ITAM is a conserved motif composed of two copies of the sequence tyrosine-X-X- leucine found in the cytoplasmic tails of various membrane proteins that are involved in signal transduction. When these receptors bind their ligand, the tyrosine residues of the ITAMs will be phosphorylated by the receptor associated tyrosine kinases in order to transmit activation signal. CD3, , Igα, Igβ,some activating rececptorsCD3, Igα, Igβ

ITIM(Immunoreceptor tyrosine- based inhibition motif): ITIM contains I/VxYxxL consensus sequence and transducts inhibitory signal.

Part Ⅱ T cell accessory molecules  Accessory molecules----- related to the activation

Part Ⅱ T cell accessory molecules 1. CD4 and CD8: co-receptor  CD4----class Ⅱ MHC （ β 2 ） Receptor of HIV  CD8----class Ⅰ MHC ( α 3 ) CD4 and CD8 also participate in signal transduction after TCR bind antigen specifically. D1 D2 D3 D4 Lck αβ

CD4 + T cell

CD4 + T cell(Th) CD8 + T cell(Tc) T cell Receptor Peptide MHC Class II T cell Receptor Peptide MHC Class I Antigen Presenting Cell Antigen Presenting Cell CD4CD8

2. Co-stimulatory receptor: CD28  CD28 on resting or activated T cells binds to the B7(CD80/CD86) on APC  Contain ITAM domain  Transduct an important co-stimulatory signal to T cells Part Ⅱ T cell accessory molecules

CTLA-4 CD40L

3. CTLA-4  CTLA-4(cytotoxic T lymphocyte antigen-4, CD152) on activated T cells binds to B7 on APC  Homologous to CD28  Bind to B7 with high affinity  Contain ITIM domain  Transmit an inhibitory signal to T cells Part Ⅱ T cell accessory molecules

4. CD2(LFA-2, Sheep red blood cell receptor)  Expressed on 90% mature T cells( none on B cells)  Its ligand is CD58(LFA-3) expressed on APC, RBC of human or sheep  Functions: Mediate the formation of E-rossete Enhance the binding of TCR and antigenic peptide-MHC molecule complex Participate in signal transduction of T cell activation Part Ⅱ T cell accessory molecules

5. LFA-1 (lymphocyte function antigen-1) CD11a/CD18 Its ligand is ICAM-1(CD54),2,3 Mediated adhesion between T cell and APC or target cell 6. VLA-4 (very late antigen-4) CD49d/CD29 Its ligand is VCAM-1,fibronectin,laminin Mediated adhesion between T cell and APC or target cell Part Ⅱ T cell accessory molecules

7. Mitogen receptor: --- Related to lymphocyte transformation test  PHA( 植物血凝素 ), ConA( 刀豆蛋白 A) ---Activating T cell only  PWM( 美洲商陆 ) ---Activating T and B cells 8. Cytokine receptor: IL-2R,IL-12R Part Ⅱ T cell accessory molecules

9. Other accessory molecules CD CD45RA: naive T cell ----CD45RO: effector T cell, memory T cell L-selectin:GlyCAM-1,CD34 CD44 Part Ⅱ T cell accessory molecules

Part Ⅲ B cell antigen receptor and B cell receptor complex  BCR  BCR complex

1. B cell receptor--BCR Membrane immunoglobulin(mIg) on B cell: mIgM, mIgD Recognize and bind antigen specifically Part Ⅲ B cell antigen receptor and B cell receptor complex

2. BCR complex BCR and Ig-  (heterodimer) Ig  (CD79a), Ig  (CD79b) Participate in BCR formation ITAM------bind to tyrosine kinase Transmit activating signal Part Ⅲ B cell antigen receptor and B cell receptor complex

3. CD19, CD21(CR2), CD81(TAPA-1) ----B cell co-receptor complex  CD21(CR2): receptor of C3dg,C3d and iC3b ----Enhance the binding of BCR and antigen and pass activating signal to CD EB virus receptor  CD19: Transmit activating signal into B cell Part Ⅲ B cell antigen receptor and B cell receptor complex

1. CD40----co-stimulatory receptor CD40 on B cell binds to CD40L on activated T cell Transmit an important co-stimulatory signal to B cells Upregulate expression of B7 on B cells Participate in class switching of antibody Part Ⅳ B cell Accessory molecules

2. B7 B7-1 (CD80) and B7-2 (CD86) Expressed on B cells or other APC B7-CD28 B7-CTLA-4 3. MHC molecules Class Ⅰ, Ⅱ MHC molecules Part Ⅳ B cell Accessory molecules

4. Mitogen receptor SPA, LPS PWM 5. Cytokine receptor IL-4R, IL-5R, IL-6R Part Ⅳ B cell Accessory molecules

Part Ⅴ T cell subpopulations and B cell subpopulations Ⅰ. T cell subpopulations Ⅱ. B cell subpopulations

Ⅰ. T cell subpopulations  According to activating stage of T cells  According to type of TCR  According to expression of CD4 or CD8  According to functions of T cell

1. According to activating stage of T cells  Na ï ve T cell  Activated T cell  Effective T cell  Memory T cell Ⅰ. T cell subpopulations

Na ï ve T cell Memory T cell Stimulation of Ag no yes IL-2R(high avidity) no yes CD45 CD45RA CD45RO MHC- Ⅱ molecule no yes ICAM no yes

2. According to type of TCR Ⅰ. T cell subpopulations

3. According to expression of CD4/CD8  CD4 + T cell  CD8 + T cell Ⅰ. T cell subpopulations

4. According to functions of T cell  Th cell(Th1,Th2,Th3,Tr1)----CD4 +  Tc cell or CTL(Tc1 and Tc2)----CD8 +  Tr cell(CD4 + CD25 + ) Ⅰ. T cell subpopulations

Th1 IL-2,IFN-γ CMI Ag CD4 + T cell Th0 Th2 IL-4,5,6 HI Th3 TGF-β Inhibitory function Tr1 IL-10 IL-12 IL-2 IFN-γ IL Functions of CD4 + Th cell Ⅰ. T cell subpopulations

Ⅱ. B cell subpopulations According to expression of CD5 or not  B1 cell (CD5 + )  B2 cell (CD5 - )

Comparison of B1 and B2 cells B1 B2 Development early late BCR mIgM mIgM and mIgD CD5 + - Reproduction self-renewing from pre-B cell in BM Recognized Ag TI-Ag and auto-Ag TD-Ag Ab type IgM >IgG IgG >IgM Ab avidity low high Second IR - + Function innate immunity adaptive immunity

Function of B cell  Produce the antibody----HI  Present antige----APC  Participate in immunological regulation Ⅱ. B cell subpopulations