Dr. ihsan edan abdulkareem alsaimary PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY ihsanalsaimary@gmail.com mobile : 009647801410838 university of basrah - college of medicine - basrah -IRAQ

1. 1
1
01/20/98
Major Histocompatability
Complex
prof.dr.ihsan edan alsaimary
department of microbiology – college
of medicine – university of basrah

2. 2
2
01/20/98
4
Major Histocompatability
Complex
 Assigned Reading
 Content Outline
 Performance Ojectives
– Key terms
– Key Concepts
 Short Answer Questions

3. 3
3
01/20/98
5
Assigned Reading
 Chapter: 9 pp 223-248
 Janis Kuby’s Immunology 3rd Ed

4. 4
4
01/20/98
6
Content Outline
 General Characteristics of MHC
 MHC Molecules & Genes
– MHC-I
– MHC-II
– MHC-III
 Genomic maps of MHC
 Cellular Distribution of MHC
 Regulation of MHC Expression
 MHC and Immune Responsiveness
 MHC and Disease

5. 5
5
01/20/98
7
General Characteristics of
MHC
 MHC vs HLA
 Congenic mice
 Genetic Co dominance
 Location & function of MHC regions
 MHC haplotypes

6. 6
6
01/20/98
MHC vs HLA
 MHC: Major Histocompatability
complex
– mouse genetic complex
 HLA: Human Leucocyte Antigen
– human genetic complex
Similar functions: different terms

7. 7
7
01/20/98
61
MHC genes (mouse)
 Class 1 genes K D L R Qa Tla
 Class 2 genes A A E E
 Class 3 genes C4 Slp

8. 8
8
01/20/98
62
HLA genes (human)
 HLA 1 B C A
 HLA 2 SB SB
 HLA 3 C4f C4S C2 Bf

9. 9
9
01/20/98
53
MHC antigens codominate

10. 10
10
01/20/98
Congenic Mice
 Two strains of mice that are genetically
identical except at one locus
 developed by successive back crosses to
one parent
 each progeny tested for specific difference
 if difference still present then back cross
again

11. 11
11
01/20/98
36
MHC: Assays
 Serotyping
 Mixed lymphocyte Reaction

12. 12
12
01/20/98
58
Public vs Private Ag

13. 13
13
01/20/98
60
Antibody production during
Transplants

14. 14
14
01/20/98
59
Antibodies during transplants
(2)

15. 15
15
01/20/98
37
Serological Tissue Typing

16. 16
16
01/20/98
38
Mixed Lymphocyte Reaction

17. 17
17
01/20/98
Mixed Lymphocyte Reaction

18. 18
18
01/20/98
56
Haplotype Restricted
Cytotoxicity

19. 19
19
01/20/98
8
MHC Molecules & Genes
 Structure of MHC-I
 Structure of MHC-II
 Gene Organization
 Peptide Binding

20. 20
20
01/20/98
9
MHC-I

21. 21
21
01/20/98
40
MHCI Carbohydrates

22. 22
22
01/20/98
41
MHC I: : 3D structure

23. 23
23
01/20/98
42
HLA I: Structure

24. 24
24
01/20/98
44
MHC I: Biological function

25. 25
25
01/20/98
10
MHC-II
 Polymorphic
 Immunocytes
 Class II molecules

26. 26
26
01/20/98
43
HLA 2: Structure

27. 27
27
01/20/98
48
MHC II: Ag Presentation
Detail

28. 28
28
01/20/98
55
Idependent vs Associative
recognition

29. 29
29
01/20/98
50
MHCII: Function

30. 30
30
01/20/98
46
MHCII: Biologogical function
(2)

31. 31
31
01/20/98
47
MHC II: Biological function

32. 32
32
01/20/98
49
MHC II: Ag Presentation

33. 33
33
01/20/98
13

34. 34
34
01/20/98
MHC III
 Collection of genes associated with
MHC
 Do not code for MHC I or MHC II
 Code for associated immunological
molecules
– complement
– interferon
– Tumour necrosis factor

35. 35
35
01/20/98
Class III MHC Products
 Gene
 C2, C4a,C4b, Bf
 COL11A2
 CYP21,CYP21P
 G7a/b
 HSP
 LMP2, LMP7
 TAP1,TAP2
 TNF-, TNF-
 Encoded Protein
 Complement
 collagen
 Steroid 21-hydroxylases
 Valyl-tRNA synthetase
 Heat Shock Protein
 Proteasome-like subunits
 Peptide transports subunits
 Tumour Necrosis factor

36. 36
36
01/20/98
11
Genomic maps of MHC
 MHC-I
 MHC-II
 MHC-III

37. 37
37
01/20/98

38. 38
38
01/20/98
52
Organization of Mouse Genes

39. 39
39
01/20/98
12
Cellular Distribution of MHC

40. 40
40
01/20/98

41. 41
41
01/20/98

42. 42
42
01/20/98
13
Regulation of MHC
Expression
 5’ promotor sequences
 Positive and negative control of
transcription
– CIITA-Transactivator
– RFX
Bare lymphocyte Syndrome

43. 43
43
01/20/98
13
Regulation of MHC
Expression
 Class I level of expression different in
various cell types
 Class II- gene expression limited to
certain cell types

44. 44
44
01/20/98
14
MHC and Immune
Responsiveness
 Determinant selection model
 Hole in the repertoire model

45. 45
45
01/20/98
15
MHC and Disease

46. 46
46
01/20/98
63
Distribution of MHC Antigens
 MHC I All nucleated cells & Platelets
(mouse RBCs)
 MHC II lymphocytes, monocytes,
macrophages

47. 47
47
01/20/98
DONE!!

48. 48
48
01/20/98
Performance Objectives

49. 49
49
01/20/98
17
Key Terms
 alleles, alloantigens. bone marrow
chimeras, Class I molecules, Class I
regions, Class II molecules,
 Class II regions, Class III molecules,
Class III regions, Determinant selection
model,
 H-2 complex and its regions D region, I
region, K region, L region, S region

50. 50
50
01/20/98
18
 hole in the repertoire models,locus,
Immune response genes, congenic mice,
Human Leukocyte Antigens, Major
histocompatibility complex, MHC
restriction, negative thymic selection
 positive thymic selection, public
specificities, private specificities, region,
Specificities, superantigens

51. 51
51
01/20/98
19
Key Concepts
 Explain the connection between a trait and a
gene using the specific example that MHC
genes encode for molecules that allow
specific immune responses.
 Describe the use of inbred mice for the
elucidation of the genetics of the imune
response
 Describe how congenic strains of mice are
developed.

52. 52
52
01/20/98
20
 Describe and draw MHC-I molecules
 Describe the function of MHC-I
molecules
 Describe and Draw MHC-II molecules
 Describe the function of MHC-II
molecules

53. 53
53
01/20/98
21
 Compare the detailed differences in the
structure of the aggreotope binding
sites of MHC-I and MHC-II
 Describe the function of class III genes
and in which cells they are expressed.
 Describe MHC restriction

54. 54
54
01/20/98
22
 Discuss the differences between MHC
restriction of CD4+ T cells and MHC
restriction of CD8+ T cells.
 Draw maps of either the MHC gene complex
in mice or HLA gene complex in humans
 Describe how the collection of MHC genes of
an individual dictates either the ability or
inability of the animal to respond to a
particular antigen

55. 55
55
01/20/98
23
 Describe an experiment that shows MHC
restriction:
– between T and B cells,
– between T cells and macrophages
– between cytotoxic T cells and virally infected cells.
 Discuss the biological relevance of MHC
molecules
 MHC molecules exhibit a range of structural
diversity at the species level that is roughly
equivalent to the range of antibody diversity at
the level of the individual animal. DISCUSS

56. 56
56
01/20/98
Short Answers

57. 57
57
01/20/98
25
 Null cells are not MHC restricted. Explain.
 Even though the immune system rejects
transplanted kidneys and hearts its function
is not to protect us against grafts. Why do we
need histocompatability antigens?
 If we do not need protection against attack
from foreign organs and tissues, why are
MHC-I molecules so polymorphic?

58. 58
58
01/20/98
26
 What is the connection between
immunity and MHC genes.?
 Why are inbread/congenic mice
important to immunlogical studies?
 Draw and label a diagram of a class I
MHC molecule as it is found in the
membrane.

59. 59
59
01/20/98
27
 Draw and label a diagram of a class II MHC
molecule as it is found in the membrane.
 How is the polymorphism or diversity of
MHC, different from the generation of
diversity in antibodies?
 How do MHC-II molecules allow immune
cells to communicate with each other?
 Why is this communication important?

60. 60
60
01/20/98
28
 What is the relationship between MHC-
II molecules and Ir genes?
 Class III MHC molecules are not cell
membrane proteins. What are they and
what do they do?
 Describe an experiment to show MHC
restricted cytotoxicity

61. 61
61
01/20/98
29
 T-cells do not recognize free antigen, as
antibody receptors do. Speculate why?
 Briefly discuss MHC restriction.
 Describe and experiment that describes
MHC restriction.
 Why do T cells have such an elaborate
way of reacting with antigen?

62. 62
62
01/20/98
30
 Explain the following statement: "There is a
direct relationship between an animal's MHC
haplotype and its ability or inability to
respond to a specific antigen."
 What is the difference between and F1 hybrid
animal and a bone marrow chimera animal?
 What is the importance of a bone marrow
chimera animal in immunological studies?
 Explain how the control of MHC restriction is
the genetic basis for the functional specificity
of T cells.

63. 63
63
01/20/98
31
 Describe T cell differentiation in the thymus
using CD4 and CD8 markers.
 T cell receptor diversity results from gene
rearrangements, but T cells are also MHC
restricted. MHC restriction is not
preprogrammed into T cells.
 Describe two possible selective processes
that program T cells to be MHC restricted.
Where do these processes occur?

64. 64
64
01/20/98
32
 T cells can react only with protein
fragments. What is this process called?
How does it occur?
 Which pathway leads to antigen
interaction with MHC-I molecules?
 Which pathway leads to interaction
with MHC-II molecules?

65. 65
65
01/20/98
54

66. 66
66
01/20/98
57
Evolution of MHCEpitopes