Chapter 12 Antigen receptors and accessory molecules of lymphocytes

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Chapter 12 Antigen receptors and accessory
molecules of lymphocytes
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Contents

• Part? T cell receptor complex
• Part? T cell accessory molecules
• Part? B cell antigen receptor and B cell receptor
  complex
• Part? B cell accessory molecules
• Part? T cell subpopulations and B cell
  subpopulations

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Part? T cell receptor complex

• Antigen receptor complex------recognizing antigen

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TCR and TCR complex
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1. TCR

• (1)Definition A kind of membrane molecules on T
  cells that can specially bind to the antigenic
  peptide-MHC molecule complex
• (2)TypesaßTCR
• ?dTCR

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• (3) Structure of TCR
• Extracellular region
• V region V ? and V ?
• antigen binding site
• CDR1,CDR2,CDR3
• C region C? and C?
• Transmembrane region
• anchoring domain
• positive charge
• Cytoplasmic region
• cant transduce signal
• (312aa)

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CDR3
CDR2
CDR1
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Three dimensional structure of TCR
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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.

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• (2) CD3 and ? chain
• Consists of ??,??, ?? or ?
• Important membrane molecules of T cells
• Pass activation signal into T cells
• Contain ITAM in the cytoplasmic region

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• 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, ?, Iga, Igß,some activating rececptors

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

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Part? T cell accessory molecules

• Accessory molecules-----related to the activation

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Part? T cell accessory molecules

• 1. CD4 and CD8 co-receptor
• CD4----class ? MHC(ß2)
• Receptor of HIV
• CD8----class ? MHC (a3 )
• CD4 and CD8 also participate in signal
  transduction after TCR bind antigen specifically.

a
ß
D1
D2
D3
D4
Lck
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CD4T cell
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Part? T cell accessory molecules

• 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

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CTLA-4 CD40L
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Part? T cell accessory molecules

• 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

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Part? 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

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Part? 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

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Part? T cell accessory molecules

• 7. Mitogen receptor
• ---Related to lymphocyte transformation test
• PHA(?????), ConA(???? A)
• ---Activating T cell only
• PWM(????)
• ---Activating T and B cells
• 8. Cytokine receptor IL-2R,IL-12R

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Part? T cell accessory molecules

• 9. Other accessory molecules
• CD45
• ----CD45RA naive T cell
• ----CD45RO effector T cell, memory T cell
• L-selectinGlyCAM-1,CD34
• CD44

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Part? B cell antigen receptor and B cell
receptor complex

• BCR
• BCR complex

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1. B cell receptor--BCR
Part? B cell antigen receptor and B cell
receptor complex

• Membrane immunoglobulin(mIg) on B cell mIgM,
  mIgD
• Recognize and bind
• antigen specifically

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Part? 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

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Part? 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 CD19
• ----EB virus receptor
• CD19 Transmit activating signal into B cell

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Part? B cell Accessory molecules

• 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

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Part? 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 ?,? MHC molecules

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Part? B cell Accessory molecules

• 4. Mitogen receptor
• SPA, LPS
• PWM
• 5. Cytokine receptor
• IL-4R, IL-5R, IL-6R

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Part? T cell subpopulations and B cell
subpopulations

• ?. T cell subpopulations
• ?. B cell subpopulations

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?. 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

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1. According to activating stage of T cells
?. T cell subpopulations

• Naïve T cell
• Activated T cell
• Effective T cell
• Memory T cell

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• Naïve T cell
  Memory T cell
• Stimulation of Ag no
  yes
• IL-2R(high avidity) no
  yes
• CD45 CD45RA
  CD45RO
• MHC-? molecule no
  yes
• ICAM no
  yes

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2. According to type of TCR
?. T cell subpopulations
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3. According to expression of CD4/CD8
?. T cell subpopulations

• CD4 T cell
• CD8 T cell

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4. According to functions of T cell
?. T cell subpopulations

• Th cell(Th1,Th2,Th3,Tr1)----CD4
• Tc cell or CTL(Tc1 and Tc2)----CD8
• Tr cell(CD4CD25)

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Functions of CD4Th cell
?. T cell subpopulations
IL-12 IL-2

• Th1
  IL-2,IFN-? CMI
  
• Ag
• CD4T cell Th0 Th2 IL-4,5,6
  HI
• Th3
  TGF-ß
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  Inhibitory
• 
  
  function
• Tr1
  IL-10

IFN-?
-
-
IL-4
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?. B cell subpopulations

• According to expression of CD5 or not
• B1 cell (CD5)
• B2 cell (CD5-)

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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 gtIgG
  IgG gtIgM
• Ab avidity low
  high
• Second IR -
  
• Function innate immunity
  adaptive immunity

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Function of B cell
?. B cell subpopulations

• Produce the antibody----HI
• Present antige----APC
• Participate in immunological regulation