Title: T cells I. T cell maturation in the thymus II. T cell receptor and T cell accessory molecules III. T cell subsets
1T cellsI. T cell maturation in the thymusII.
T cell receptor and T cell accessory
moleculesIII. T cell subsets
2I. T cell maturation in the thymus1. Process2.
Events
31.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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52.events1) rearrangement of TCR gene2)
positive selection and negative selection
6Rearrangement 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
7- (1) Germ-line Gene structure of TCRaß
- achain(14 chromosome) V, J, C
- ßchain(7 chromosome) V, D, J, C
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10- (2) Gene rearrangement of TCRaß
- achain
- VJ VJ-C VJC
- DNA RNA mRNA
- ß chain
- DJ VDJ VDJ-C VDJC
- DNA RNA
mRNA
11 12(3) Characteristics of the rearrangment of TCR
genesallelic exclusion
13(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
14Comparison 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 - --------------------------------------------------
-----------------------
152) positive selection and negative selectionMHC
restriction self tolerance
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20Positive 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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22Negative 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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28II. T cell receptor and T cell accessory
molecules
- T cell receptor complex
- T cell accessory molecules
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31TCR complex, Co
receptor, Co-stimulator receptor,
immunological synapse
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33- 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 ??)
34- 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
35- CD3 consisting of ??,??, ?? or ?? contain
ITAMs, pass signal into cells - ITAM immune receptor tyrosine-based activation
motif-----transduce activation signals from TCR
36a??? Alpha ß?? Beta ??? Gamma d??? Delte
e???? Epsilon ? ?? Zeta ??? Eta
37- 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
38- 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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41Promote the signal transduction
42CD28 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
43- 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.
44- 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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48- 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.
49 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
50naive 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
51Classification according to TCR
52Comparison 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 - --------------------------------------------------
---------------------------- -
53Classification according to CD4/CD8
- CD3CD4CD8-T --CD4T MHC-II
- CD3CD4-CD8T--CD8T MHC-I
54 Classification according to T cell function
- 1.Th (help T cells)
- (Th1, Th2)----CD4
- 2.Tc ( CTL)
- ----CD8
- 3. Treg
- ----CD4, CD25 , Foxp3
55T 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