?12? ?????????????? Antigen Receptors

1
?12? ??????????????Antigen Receptors
Accessory Molecules of Lymphocytes
2
Contents

• T???????
• T??????
• B???????
• B??????

3
??? T????????? T cell Receptor complex

• TCR
• CD3???

4

• T???????
• (T cell receptor complex)
• TCR
• CD3??-????

5
??TCR

• T?????????
• T??????
• ?????Ag(Ag?-MHC???)
• T?????????
• ??TCR
• ??TCR

6
1.?? TCR

• ???????
• ???
• V?
• C?
• ???
• ????????
• ???
• ?

7
(No Transcript)
8
(No Transcript)
9
TCR
Antigen combining site
Resembles an Ig Fab fragment
Va
Vb
Ig gene superfamily
Carbohydrates
Antigen combining site made of Va and Vß regions
Ca
Cb
Hinge
constant regions


Heterodimeric, chains are disuphide-bonded

Positively charged amino acids in the TM region
Very short intracytoplasmic tail
10

• V?
• 3?CDR3
• CDR3?????
• CDR1?CDR2???-MHC?????a??

11
(No Transcript)
12
2. ?? TCR

• ??????
• ???????
• ?????????TCR?

13
??CD3???

• ??T????
• ??TCR??,??T??????
• 6????????? ?????
• ?????????Ig???
• ?????ITAM

14
TCR-CD3 complex
The intracytoplasmic region of TCR chain is too
short to transduce a signal

• The CD3????????or ? ?chains are required for
• Cell surface expression of the TCR-CD3 complex
• Signalling through the TCR

15
(No Transcript)
16
Transduction of signals by the TCR
The cytoplasmic domains of the CD3 complex
contain 10 Immunoreceptor Tyrosine -based
Activation Motifs (ITAMS) YXXL/VX7-11YXXL/V
ITAMs are involved in the transmission of the
signals from the receptor and require clustering
of TCR/CD3 and the CD4 or CD8 co-receptors
17

• ???????????
• (immune receptor tyrosine based activation
  motifs, ITAM)
• ???YXX(L/V)X7-11YXX(L/V)
• ???????????????,????????????,??????

18
??? T?????? T Cell Accessory Molecules

• CD4
• CD8
• CD28
• CTLA-4

• CD45
• CD2
• CD44
• LFA-1

• VLA-4
• L-???
• ?????
• ??????

19

• ????
• ??T????
• ????
• ??T????
• ????????

20
??CD4?CD8??---????

• Co-receptor
• CD4
• CD8

21
(No Transcript)
22
1?CD4??

• 65????????T??,???Th
• ???????DC???????
• ???????
• D1-D4???
• ?MHC????ß2??????

23

• ??
• ??TCR?Ag?-MHC???????
• ??T???????
• ?CD4T???-MHC???

24
2?CD8??

• ??Tc
• ?/????
• 2?IgG V???
• ?MHC????a3??????

25

• ??
• ??TCR?Ag?-MHC???????
• ??T???????
• ?CD8T??Ag?-MHC???

26
T cell co-receptor
27
CD8 and CD4 contact points on MHC class I and
class II
28
??CD28???????

• CD28
• CD2
• LFA-1

29
1?CD28

• 90CD4T,50CD8T
• ?????,?Ig???
• ????ITAM
• ???CD80/CD86(B7)
• CD28/B7???T??????????

30
2?CTLA-4

• ??T????
• ?????,?CD28????
• ????ITIM
• ????B7
• CTLA-4/B7??????T????,???

31

• CTLA-4?CD28??
• ??T?????,????T?????
• ?B7?????CD28?20?
• ?????ITIM,?B7?????????????,??T????

32
CTLA-4?CD28
Induces CTLA-4
CTLA-4 binds CD28 with a higher affinity than B7
molecules
33

• ???????????
• (immune receptor tyrosine based inhibitory motif,
  ITIM)
• ?????????(??SHIP),?????????????????

34
(No Transcript)
35
3?CD2

• LFA-2,???????
• 90????T????????NK
• ????2????
• ???LFA-3
• CD2/LFA-3?????????????

36
Erythrocyte Rosette Forming Cell Assay

• How to detect T lymphocytes?

T cells
CD2
37
4?LFA-1

• ??T????????B???????????
• ???ICAM-1
• ????

38
?? ?????

• CD45
• CD44
• VLA-4
• L-???
• ?????
• ??????

39
1? CD45

• ???????
• ????????,??T??????
• ?CD4?CD8????
• CD45RA???T??
• CD45RO??T???T??

40
2??????

• ???(mitogens)
• ?????????T?B????
• ?????????????,?????????
• ?PHA?ConA?PWM

41
Clone B
Clone A
?????
42
(No Transcript)
43
(No Transcript)
44
T??????

• T???????
• T??????
• T????????
• ???????

45
??? B???????B Cell Receptor Complex

• BCR
• Iga/Igß

46

• B???????
• BCR
• Iga/Igß

47
??BCR

• B?????????
• B??????
• ?????Ag
• ????????(mIgM?mIgD)
• ???
• ???
• ???

48
??Iga/Igß

• ?????,????ITAM
• ??BCR?????
• ??B?????????

49
Transduction of signals by the B cell receptor
50
??? B?????? B Cell Accessory Molecules

• MHC??
• ?????
• ??????

• CD19
• CD21
• CD81

• CD40
• CD45
• B7

51
??CD19/CD21--???????

• CD21(CR2)
• ???C3d
• ??BCR??????
• CD19
• ????,?ITAM
• ??BCR?????B??????

52
B cell co-receptor
CD45
53
C3d opsonised bacterium
P
P

• BCR and CD21 are cross-linked by antigen that has
  activated complement

• Ligation of the co-receptor increases BCR
  signalling 1000 -10,000 fold

54
(No Transcript)
55
??CD40???????

• CD40
• B?????APC??
• CD40/CD40L???B??????????

56
???????

• CD45
• ????????,??B????
• B7
• B7/CD28??,?T????????????

57

• MHC??
• ?????
• ??????

58
(No Transcript)
59
(No Transcript)
60
B???????

• BCR???
• ???????
• ??????
• ?????

61
??? T???B????Classification of T cells and B
cells
62
??T????

• ??T??????????
• ??T?????T??
• CD4?CD8T??
• Th1?Th2??

63
(No Transcript)
64
T??
aßT??
?dT??
CD4T??
CD8T??
CD4CD25T??
Th
CTL
Th2
Th1
65
(No Transcript)
66
(No Transcript)
67
(No Transcript)
68
??B????

• B1??(CD5)
• B2??(CD5-)

69
Two B cell lineages
B2 cells
B1 cellsPrimitive B cells found in pleura and
peritoneum
IgM - no other isotypes