1. Major Histocompatibility Complex Molecules
1. Structure of MHCs and their polygeny
2. Polymorphisim of MHC
3. Interaction of MHC molecule and antigenic peptide
4. HLA and clinical medicine
5. Biological functions of MHC

4. Section 1: Structure of MHCs and their polygeny
Polygeny is defined as MHC complex that comprises many adjacent gene locus, encoding proteins with same or similar functions.
MHC is divided into three categories.

5. （一）Classical MHC I and MHCII molecules
mouse H-2
Human HLA
Chromosome location 17
1500kb
6p21.31
3600kb I
K、D、L
B、C、A II
A、E
DP、DQ、DR
III C
C4 A BfC2

6. Structure of H-2
Structure of HLA

7. Schematic diagram of HLA embryonic genes
class II
class III
class I
class I
centromere
Schematic diagram of HLA embryonic genes

8. （二） HLA molecules encoded by MHC I and II genes
1. Distributions ：
Class I (HLA-A/B/C): all nucleated cells
Class II (HLA-DR/DP/DQ): APC(Mf,DC,B), thymic epithelial cells, activated T cells
2. Structure：
Class I :  ( 1  2  3 Tm C), 2m
Class II:  ( 1  2 Tm C),  ( 1  2 Tm C)

10. membrane
Class I MHC molecules
MHC I类分子

11. Schematic diagram of MHC I molecules

13. membrane
Class II MHC molecules
MHC II类分子

14. Schematic diagram of MHC II molecules

15. MHC class I molecule
MHC class II molecule
Peptide-binding domain
Immunoglobin-like domain
Transmembrane segment
Cytoplasm
ic tail

16. 1. Genes encoding serum complement components ：
（三）Immune related genes
1. Genes encoding serum complement components ：
C4B、C4A、Bf、C2

17. 2. Genes associated with antigen processing and presentation
Gene encoding low molecular weight polypeptide(LMP)
Gene encoding transporter associated with antigen processing（TAP）
HLA-DM gene
HLA-DO gene
Gene encoding TAP associated proteins tapasin

18. 3. Non-classical MHC I（Ib）genes： HLA-E, HLA-G, HLA-F

19. 4、Inflammation associated genes
Tumour necrosis factor gene family
TNF、LTA、LTB
Transcriptional regulating gene or transcriptional factor-like gene family I-B、B144、ZNF173、ZNF178
MHC I related gene（MIC）family
Hot shock protein gene family
HSP70（molecular chaperone）

20. Immune related genes Related encoding products
Inflammation related genes
Genes encoding complement components
Genes associated with antigen processing and presentation
non-classical
MHC I genes
Related encoding products

21. Section 2: Polymorphism of MHC
（一）The basic concepts of polymorphism

22. Polymorphism: several alleles located on a single gene locus
Haplotype: A set of genetic determinants located on a single chromosome
Genotype: A set of genetic determinants located on both chromosomes
Phenotype: The expressed characteristics of an individual
Non-polymorphism, Homozygote, Heterozygote

23. Haplotype heredity of HLA

24. Phenotype,genotype and haplotype of HLAB C
Tester
Phenotype
Genotype
Haplotype

25. The Locus with the largest number of alleles are HLA-B（301）and HLA-DRB1（227）
HLA-A*0103
HLA-DRB1*1102

26. I MHC class II molecules MHC class I molecules
Polymorphism of MHC genes

27. （二）Linkage disequilibrium and haplotype
HLA-DRB1* %
HLA-DQB1* %
Probability of the two genes on the same chromosome: 3.4%
The fact is 11.3%
The Han nationality:
A2-B46-Cw3-DR9-DQ9-Dw23
A33-B17-Cw2-DR3-DQ2-Dw3

28. （三）The origin of HLA Polymorphism and its significance
Gene mutation
Gene recombinant
Gene switch
Selection pressure

29. Section 3: Interaction between MHC molecule and antigenic peptide
peptide binding cleft
peptide binding cleft

30. Specificity and flexibility of the binding
（一）Molecular basis for the interaction between MHC molecule and antigenic peptide
Topography of conformational space
Anchor residue
Consensus motif
Specificity and flexibility of the binding

31. Anchor residue
MHC molecules
Anchor

32. peptide-MHC II complex
peptide-MHC I complex
Antigenic peptide
MHC I molecules
peptide-MHC II complex
Antigenic peptide
MHC II molecules
Schematic diagram of the interaction between peptides and MHC I, II molecules

33. Products of different HLA alleles selectively bind antigen peptides with specific consensus motif
products of alleles
Class I molecules
Class II molecules

34. （二）Characteristic of the interaction between antigenic peptide and MHC molecules
Flexibility：
X amino acids which compose consensus motif can be variable in sequence and conformation .
Anchor residues which the same MHC molecule demands can be more than one amino acid
Antigenic peptides which bind different MHC molecules can have similar consensus motif.

35. Section 4 HLA and clinical medicine
1. HLA and transplantation
2. Abnormal expression of HLA and clinical diseases HLA
3. Association between HLA and diseases HLA
4. HLA and medical jurisprudence

36. Disease Relative risk Ankylosing spondylitis Acute anterior uveitis
Associated HLA allele
Relative risk
Ankylosing spondylitis
Acute anterior uveitis
Goodpasture’ syndrome
Multiple sclerosis
Gluten-sensitive enteropathy
Exophthalmic goiter
Myasthenia gravis
Systemic lupus erythematosus
Insulin-dependent diabetes mellitus
Rheumatoid arthritis
Chronic pemphigus
Hashimoto's disease
Some autoimmune diseases associated significantly with HLA alleles

37. Section 5 Biological functions of MHC
（一）Involved in adaptive immune responses as antigen presenting molecules
Double recognition of peptide and MHC by T cell through TCR
Components bound by MHC and being presented can be self antigen, and even be MHC itself.
MHC is the main determinant of individual susceptibility for certain disease.
MHC is involved in the heterogenecity of species gene structure.

41. （二）Involved in innate immune response as regulating molecules
Classical MHC III encoding complement components is involved in complement reaction and immune diseases
Products of non-classical MHC I and MIC gene can act as ligands, regulating the activities of NK cells and some killer cells
Inflammation related genes are involved in the initiation and regulation of inflammation, and play roles in stress responses.

42. To master concepts of MHC
To master the molecular structure, tissue distribution and functions of human classical MHC genes
To be familiar with the structure and characteristic of MHC genes
To be familiar with the interaction between MHC molecules and antigenic peptide.
To understand immune related genes
To understand the roles of HLA in medicine and their significances