T cells

I. T cell maturation in the thymus

II. T cell receptor and T cell accessory molecules

III. T cell subsets

I. T cell maturation in the thymus

1. Process2. Events

1.Process1) pro T cells CD3

- TCR- CD4- CD8

-

TCR β chain starts to rearrange DN

2) pre T cellsCD3

+ TCRpTα:β CD4+ CD8

+

3) immature T cells DP CD3

+ TCR+ CD4+ CD8

+ the rearrangement of TCR α chain

4) mature T cells CD3

+ TCR+ CD4+

or CD3+ TCR+ CD8

+ SP

TCR

Pre-T

Vpre-T ？

信号转导

Lck， ZAP-70， Syk

Pre-TCR

2.events

1) rearrangement of TCR gene

2) positive selection and negative selection

1) 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

(1) Germ-line Gene structure of TCRαβ

αchain(14 chromosome): V, J, C

βchain(7 chromosome): V, D, J, C

(2) Gene rearrangement of TCRαβ

αchain: VJ VJ-C VJC DNA RNA mRNA

β chain:

DJ VDJ VDJ-C VDJC DNA RNA mRNA

(3) Characteristics of the rearrangment of TCR genes

allelic exclusion

(4) The mechanism of diversity of TCR

1). Mutiple germline gene segments2). Combinatorial V(D)J joining3). Junctional flexibility imprecise joining and N-nucleotides addition 4). combinatorial assocination of α andβ chain

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 -------------------------------------------------------------------------

2) positive selection and negative selection

MHC restriction self tolerance

CD3‾CD4+ CD8‾ TCR‾ CD3‾CD4‾CD8+ TCR‾

CD3LOWCD4‾CD8+ TCRLOW

CD3+ CD4+ CD8+ TCR+

CD3+ CD4+ CD8‾ TCR+ CD3+ CD4‾ CD8+ TCR+

CD3+ CD4+ TCR+ CD3+ CD8+ TCR+

CD3+ CD4+ CD8+ TCR+

CD3+ CD4+ CD8‾ TCR+

CD3+ CD4‾ CD8+ TCR+

CD3+ CD4‾ CD8‾ TCR+

CD3+ CD4‾ CD8‾ TCR+

CD3+ TCR+

CD3‾CD4‾/LOW CD8‾ TCR‾

CD3‾CD4‾/LOW CD8‾ TCR‾

被膜

被膜下区

皮质

骨髓

髓质

胸腺小叶

Positive selection DP cells whose TCR can recognize and combine wit

h peptide-MHC molecule complexes expressed on the cortical epithelial cells in an appropriate affinity differentiate continuously to become SP cells.

DP cells whose TCR can’t 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 selec

tion: MHC-I-------CD8+ expression MHC-II------CD4+ expression

Negative seletion SP cells whose TCR can’t combine with peptid

e-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

II. T cell receptor and T cell accessory molecules

T cell receptor complex

T cell accessory molecules

TCR complex, Co –receptor,

Co-stimulator receptor, immunological synapse

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 η)

TCR: a kind of membrane molecule on T cells that can specially bind to the antigen (Recognize specifically with Ag-MHC complex)

αβTCR

External segment

------V region, C region

Transmembrane segment

Cytoplasmic segment

γδTCR

CD3: consisting of ,, or η contain ITAMs, pass signal into cells

ITAM: immune receptor tyrosine-based activation motif-----transduce activation signals from TCR

α ：阿尔法 Alpha β ：贝塔 Beta γ ：伽玛 Gamma δ ：德尔塔 Delte ε ：艾普西龙 Epsilon ζ ：捷塔 Zeta η ：依塔 Eta

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

co-receptors

CD4 and CD8 CD4—MHC-II （ β2）

CD8----MHC-I (α3 )

Assist to recognize antigens

Promote the activation of T cells

Promote the signal transduction

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

CD40L

CD40L --- CD40 on B cell

---transduce a co-stimulatory signal to B cells

CD45A cell surface glycoprotein with a cytoplasm

ic tyrosine phosphatase domain, is believed to play a role in T cell activation.

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).

Mitogen receptor

PHA(phytohemagglutinin),ConA(concanavalin A) ------activating T cell only

PWM(pokeweed mitogen) -----activating T and B cells

lymphocyte transformation test

Cytokine receptorIL-1R, IL-2R etc.

III. Subsets of T cells

according to activationnaive T cells, effective T cells and memory T cells

according to TCR T and T

according to CD4/CD8CD8+ Tcells, CD4+ Tcells according to fuctionsTh, Tc/CTL and Treg

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 cellstimulation of Ag no yesIL-2R no yesCD45 CD45RA CD45RO MHC-II no yes ICAM no yes

Ag

Classification according to TCR

T cells:

T cells:

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

------------------------------------------------------------------------------

Classification according to CD4/CD8

CD3+CD4+CD8-T --CD4+T: MHC-II

CD3+CD4-CD8+T--CD8+T: MHC-I

 Classification according to T cell function

1.Th (help T cells):

(Th1, Th2)----CD4+

2.Tc ( CTL):

----CD8+

3. Treg:

----CD4+, CD25+ , Foxp3+

T cells

1. 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