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

2. I. T cell maturation in the thymus 1. Process 2. Events

3. 1.Process 1) pro T cells CD3- TCR- CD4- CD8- TCR β chain starts to rearrange DN 2) pre T cells CD3+ 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+ CD SP

4. TCR b
Pre-Ta
Vpre-T？
g e e d
信号转导
Lck，ZAP-70，Syk
Pre-TCR

5. 2.events 1) rearrangement of TCR gene 2) positive selection and negative selection

6. 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

7. (1) Germ-line Gene structure of TCRαβ
αchain(14 chromosome): V, J, C
βchain(7 chromosome): V, D, J, C

10. (2) Gene rearrangement of TCRαβ αchain:
VJ VJ-C VJC
DNA RNA mRNA
β chain:
DJ VDJ VDJ-C VDJC
DNA RNA mRNA

12. (3) Characteristics of the rearrangment of TCR genes allelic exclusion

13. (4) The mechanism of diversity of TCR 1)
(4) The mechanism of diversity of TCR 1). Mutiple germline gene segments 2). Combinatorial V(D)J joining 3). Junctional flexibility imprecise joining and N-nucleotides addition 4). combinatorial assocination of α andβ chain

14. Comparison of BCR and TCR functional genes
NO. of chain Chromosome V D J C
BCR H  
TCR    

15. 2) positive selection and negative selection MHC restriction self tolerance

16. 胸腺小叶 被膜 被膜下区 皮质 髓质 骨髓 CD3‾CD4‾/LOW CD8‾ TCR‾ CD3‾CD4+ CD8‾ TCR‾
CD3LOWCD4‾CD8+ TCRabLOW
CD3+ CD4+ CD8+ TCRab+
CD3+ CD4+ CD8‾ TCRab+
CD3+ CD4‾ CD8+ TCRab+
CD3+ CD4+ TCRab+
CD3+ CD8+ TCRab+
CD3+ CD4+ CD8+ TCRgd+
CD3+ CD4+ CD8‾ TCRgd+
CD3+ CD4‾ CD8+ TCRgd+
CD3+ CD4‾ CD8‾ TCRgd+
CD3+ TCRgd+
CD3‾CD4‾/LOW CD8‾ TCR‾ 被膜
被膜下区 皮质 骨髓 髓质
胸腺小叶

20. 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 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 selection:
MHC-I CD8+ expression
MHC-II------CD4+ expression

22. Negative seletion
SP cells whose TCR can’t 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

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

31. TCR complex, Co –receptor,
Co-stimulator receptor, immunological synapse

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 η)

34. 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

35. CD3: consisting of ,,  or η contain ITAMs, pass signal into cells
ITAM: immune receptor tyrosine-based activation motif-----transduce activation signals from TCR

36. 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

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 CD4—MHC-II （β2） CD8----MHC-I (α3 )
Assist to recognize antigens
Promote the activation of T cells

41. Promote the signal transduction

42. 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 cell ITIM

43. CD40L CD40L --- CD40 on B cell CD45
---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).

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 cells according to activation naive T cells, effective T cells and memory T cells according to TCR  T and  T according to CD4/CD8 CD8+ Tcells, CD4+ Tcells according to fuctions Th, Tc/CTL and Treg

50. 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
CD CD45RA CD45RO
MHC-II no yes
ICAM no yes Ag

51. Classification according to TCR
 T cells:
 T cells:

52. Comparison of  T and  T
Characteristics  T cells  T cells
TCR more diversity less diversity
peripherial blood % %
tissue peripherial lymphoid mucosa epithelia
tissue

53. Classification according to CD4/CD8
CD3+CD4+CD8-T --CD4+T: MHC-II
CD3+CD4-CD8+T--CD8+T: 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+

55. T cells 1. stages of T cell maturation in the thymus 2
T cells 1. stages of T cell maturation in the thymus 2. mechanisms of TCR diversity 3. positive selection and negative selection 4. TCR complex and some T cell accessory molecules 3. T cell subsets