T cells I. T cell maturation in the thymus II. T cell receptor and T cell accessory molecules III. T cell subsets - PowerPoint PPT Presentation

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T cells I. T cell maturation in the thymus II. T cell receptor and T cell accessory molecules III. T cell subsets

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T cells I. T cell maturation in the thymus II. T cell receptor and T cell accessory molecules III. T cell subsets (1) Germ-line Gene structure of TCR chain(14 ... – PowerPoint PPT presentation

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Title: T cells I. T cell maturation in the thymus II. T cell receptor and T cell accessory molecules III. T cell subsets


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T cellsI. T cell maturation in the thymusII.
T cell receptor and T cell accessory
moleculesIII. T cell subsets
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I. T cell maturation in the thymus1. Process2.
Events
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1.Process1) pro T cells CD3- TCR- CD4- CD8-
TCR ß chain starts to rearrange DN2)
pre T cellsCD3 TCRpTaß CD4 CD8 3) immature
T cells DP CD3
TCR CD4 CD8 the rearrangement of TCR a chain
4) mature T cells CD3 TCR CD4 or CD3
TCR CD8 SP
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2.events1) rearrangement of TCR gene2)
positive selection and negative selection
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Rearrangement of TCR gene(1) germline gene
structure of TCR(2) rearrangement of TCR genes
(3) characteristics of the rearrangement of TCR
genes(4) The mechanism of diversity of TCR
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  • (1) Germ-line Gene structure of TCRaß
  • achain(14 chromosome) V, J, C
  • ßchain(7 chromosome) V, D, J, C

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  • (2) Gene rearrangement of TCRaß
  • achain
  • VJ VJ-C VJC
  • DNA RNA mRNA
  • ß chain
  • DJ VDJ VDJ-C VDJC
  • DNA RNA
    mRNA

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(3) Characteristics of the rearrangment of TCR
genesallelic exclusion
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(4) The mechanism of diversity of TCR1).
Mutiple germline gene segments2). Combinatorial
V(D)J joining3). Junctional flexibility
imprecise joining and N-nucleotides addition 4).
combinatorial assocination of a andß chain
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Comparison of BCR and TCR functional genes
  • NO. of chain Chromosome V D
    J C
  • --------------------------------------------------
    ---------------------
  • BCR H 14
    48 23 6 10
  • ? 2
    40 0 5 1
  • ? 22
    30 0 4 4
  • TCR ? 14
    50-100 0 100 1
  • ? 7
    20 2 14 2
  • ? 7
    7 0 4 4
  • ? 14
    5 2 6 1
  • --------------------------------------------------
    -----------------------

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2) positive selection and negative selectionMHC
restriction self tolerance
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Positive selection
  • DP cells whose TCR can recognize and combine with
    peptide-MHC molecule complexes expressed on the
    cortical epithelial cells in an appropriate
    affinity differentiate continuously to become SP
    cells.
  • DP cells whose TCR cant combine with
    pepetide-MHC molecule complexes or can combine
    with them in a high affinity go apoptosis
  • Get MHC restriction
  • MHC molecules play important role in positive
    selection
  • MHC-I-------CD8 expression
  • MHC-II------CD4 expression

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Negative seletion
  • SP cells whose TCR cant combine with peptide-MHC
    complexes expressed on the DC or macrophages
    tightly develop and differentiate continuously
  • SP cells whose TCR recognize and combine with
    self antigen peptide MHC complexes tightly go
    apoptosis
  • Acquired the self tolerance

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II. T cell receptor and T cell accessory
molecules
  • T cell receptor complex
  • T cell accessory molecules

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TCR complex, Co
receptor, Co-stimulator receptor,
immunological synapse
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  • 1.TCR cell receptor complex
  • a group of membrane molecules on T cells that can
    specially bind to the antigen and pass an
    activation signal into the cells, consisting of
    TCR (??,??) and CD3(??, ??, ?? or ??)

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  • TCR a kind of membrane molecule on T cells that
    can specially bind to the antigen (Recognize
    specifically with Ag-MHC complex)
  • aßTCR
  • External segment
  • ------V region, C region
  • Transmembrane segment
  • Cytoplasmic segment
  • ?dTCR

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  • CD3 consisting of ??,??, ?? or ?? contain
    ITAMs, pass signal into cells
  • ITAM immune receptor tyrosine-based activation
    motif-----transduce activation signals from TCR

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a??? Alpha ß?? Beta ??? Gamma d??? Delte
e???? Epsilon ? ?? Zeta ??? Eta
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  • 2. T cell accessory molecules
  • (1) co-receptors ---CD4 and CD8
  • (2)costimulatory molecule receptors
  • ----CD28, CTLA-4
  • (3) CD40L
  • (4) CD45
  • (5) CD2
  • (6) mitogen receptor
  • (7) Cytokine receptor

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  • co-receptors
  • CD4 and CD8
  • CD4MHC-II (ß2)
  • CD8----MHC-I (a3 )
  • Assist to recognize antigens
  • Promote the activation of T cells

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Promote the signal transduction
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CD28 bind to the B7(CD80/CD86) on APC
(antigen-presenting cell)----transduce a
co-stimulatory signal to T cell CTLA4(cytotoxic
T lymphocyte antigen-4, CD152) bind to B7 on
APC ---transduce a inhibitory signal to T
cellITIM
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  • CD40L
  • CD40L --- CD40 on B cell
  • ---transduce a co-stimulatory signal to B cells
  • CD45
  • A cell surface glycoprotein with a cytoplasmic
    tyrosine phosphatase domain, is believed to play
    a role in T cell activation.

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  • CD2(erythrocyte receptor)
  • ----E-rosette test
  • CD2---IFA-3(CD58) promote the cells contact
    each other.
  • LFA-1
  • lymphocyte function associate antigen 1
    its ligand is ICAM (intercellular adhesion
    molecule).

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  • Mitogen receptor
  • PHA(phytohemagglutinin),
  • ConA(concanavalin A)
  • ------activating T cell only
  • PWM(pokeweed mitogen)
  • -----activating T and B cells
  • lymphocyte transformation test
  • Cytokine receptor
  • IL-1R, IL-2R etc.

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III. Subsets of T cellsaccording to
activationnaive T cells, effective T cells and
memory T cellsaccording to TCR ?? T and ?? T
according to CD4/CD8CD8 Tcells, CD4 Tcells
according to fuctionsTh, Tc/CTL and Treg
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naive T cell and memory T cell
  •                      
  • naive T cell-----activated T cell----------
  • effective T cell and memory T cell
  • naïve T cell
    memory T cell
  • stimulation of Ag no
    yes
  • IL-2R no
    yes
  • CD45 CD45RA CD45RO
  • MHC-II no
    yes
  • ICAM no
    yes

Ag
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Classification according to TCR
  • ?? T cells
  • ?? T cells

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Comparison of ?? T and ?? T
  • -------------------------------------------------
    ----------------------------
  • Characteristics ?? T cells
    ?? T cells
  • --------------------------------------------------
    -----------------------------
  • TCR more diversity
    less diversity
  • peripherial blood 85-95
    5-15
  • tissue peripherial lymphoid
    mucosa epithelia

  • tissue
  • --------------------------------------------------
    ----------------------------


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Classification according to CD4/CD8
  • CD3CD4CD8-T --CD4T MHC-II
  • CD3CD4-CD8T--CD8T MHC-I

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 Classification according to T cell function
  • 1.Th (help T cells)
  • (Th1, Th2)----CD4
  • 2.Tc ( CTL)
  • ----CD8
  • 3. Treg
  • ----CD4, CD25 , Foxp3

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T cells1. stages of T cell maturation in the
thymus2. mechanisms of TCR diversity3. positive
selection and negative selection 4. TCR complex
and some T cell accessory molecules3. T cell
subsets
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