MHC

1. Major Histocompatability
Complex
Molecular chaparones
Dr.S.K.Barolia

2. Major Histocompatability Complex
 Assigned Reading
 Content Outline
 Performance Ojectives
◦ Key terms
◦ Key Concepts
 Short Answer Questions

3. 5
Assigned Reading
 Chapter: 9 pp 223-248
 Janis Kuby’s Immunology 3rd Ed

4. 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. 7
General Characteristics of
MHC
 MHC vs HLA
 Congenic mice
 Genetic Co dominance
 Location & function of MHC regions
 MHC haplotypes

6. MHC vs HLA
 MHC: Major Histocompatability complex
◦ mouse genetic complex
 HLA: Human Leucocyte Antigen
◦ human genetic complex
Similar functions: different terms

7. 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. 62
HLA genes (human)
 HLA 1 B C A
 HLA 2 SB SB
 HLA 3 C4f C4S C2 Bf

9. 53
MHC antigens codominate

10. 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. 36
MHC: Assays
 Serotyping
 Mixed lymphocyte Reaction

12. 58
Public vs Private Ag

13. 60
Antibody production during
Transplants

14. 59
Antibodies during transplants
(2)

15. 37
Serological Tissue Typing

16. 38
Mixed Lymphocyte Reaction

17. Mixed Lymphocyte Reaction

18. 56
Haplotype Restricted
Cytotoxicity

19. 8
MHC Molecules & Genes
 Structure of MHC-I
 Structure of MHC-II
 Gene Organization
 Peptide Binding

20. 9
MHC-I

21. 40
MHCI Carbohydrates

22. 41
MHC I: : 3D structure

23. 42
HLA I: Structure

24. 44
MHC I: Biological function

25. 10
MHC-II
 Polymorphic
 Immunocytes
 Class II molecules

26. 43
HLA 2: Structure

27. 48
MHC II: Ag Presentation Detail

28. 55
Idependent vs Associative
recognition

29. 50
MHCII: Function

30. 46
MHCII: Biologogical function
(2)

31. 47
MHC II: Biological function

32. 49
MHC II: Ag Presentation

33. 13

34. 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. 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. 11
Genomic maps of MHC
 MHC-I
 MHC-II
 MHC-III

38. 52
Organization of Mouse Genes

39. 12
Cellular Distribution of MHC

42. 13
Regulation of MHC
Expression
 5’ promotor sequences
 Positive and negative control of
transcription
◦ CIITA-Transactivator
◦ RFX
Bare lymphocyte Syndrome

43. 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. 14
MHC and Immune
Responsiveness
 Determinant selection model
 Hole in the repertoire model

45. 15
MHC and Disease

46. 63
Distribution of MHC Antigens
 MHC I All nucleated cells & Platelets
(mouse RBCs)
 MHC II lymphocytes, monocytes,
macrophages

47. Performance
Objectives

48. 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

49. 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

50. 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.

51. 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

52. 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

53. 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

54. 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

55. 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?

56. 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.

57. 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?

58. 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

59. 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?

60. 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.

61. 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?

62. 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?

63. 54

64. 57
Evolution of MHCEpitopes