1. Chapter 7. 주조직적합성 복합체 1. 주조직적합성 복합체 (MHC)의 발견 2. MHC 분자의 구조
- MHC (Major histocompatibility complex): gene complex responsible for rejection process
- Two different MHC classes: class I and class II
- Peptides from extracellular protein bind to MHC class II helper T cell recognize the complex
- Peptides from intracellular protein bind to MHC class I cytotoxic T cell recognize the complex
1) Mouse
- Histocompatibility-2 (H-2): chromosome 17
- K, D, and L region: encode MHC class I
- I region (I-A and I-E): encode MHC class II
2) Human
- Human leukocyte antigen (HLA): chromosome 6
- A, B, and C region: encode MHC class I
- D region (D-P, D-Q, and D-R): encode MHC class II
2. MHC 분자의 구조
1) MHC class I molecule
- Present on the surface of all the nucleated cells
- consist of  chain (44-47 kDa) and β chain (12 kDa)
-  chain: encoded by MHC
- β chain (β2-microglobulin): non-MHC coded
-  chain is divided into four separate regions: peptide-binding region, Ig-like region, transmembrane region and cytoplasmic region
a) The peptide-binding region
- 1 and 2 domain of  chain
- 1 domain: consist of one  helix and four β-pleated sheets
- 2 domain: consist of one  helix and four β-pleated sheets

2. - Two  helices and eight β sheets form a cleft
- The cleft: appropriate size (25Å x 10Å x 11Å) to bind a 9-11 amino acid peptide
- 1 and 2 domains are polymorphic
- Interact with TcR of Tc cell
b) The immunoglobulin-like region
- Consist of 3 domain of  chain and β2-microglobulin
- folded to form Ig-like domains
- Non-polymorphic
- 3 domain interacts with CD8 of T cell
- Interaction of β2-microglobulin with 1, 2, and 3: critical for maintaining native structure
c) The transmembrane region
- 25 aa residue stretch of hydrophobic amino acids form an  helix pass through the hydrophobic membrane
d) The cytoplasmic region
- C-terminal 30 aa residue
- Has consensus phosphorylation site for protein kinase A and pp60 src tyrosine kinase
2) MHC class II molecule
- Present on the surface of macrophage, B cell, dendritic cell, endothelial cell and epithelial cell of thymus
- Consist of  chain (32-34 kDa) and β chain (29-32 kDa)
-  and β chains are divided into four separate regions: peptide-binding region, Ig-like region, transmembrane region and cytoplasmic region
a) The peptide-binding region
- Consist of 1 domain of  chain and β1 domain of β chain
- 1 domain: consist of one  helix and four β-pleated sheets
- β1 domain: consist of one  helix and four β-pleated sheets
- The cleft: appropriate size to bind about 15 amino acid peptide
- β1 is polymorphic
- Interact with TcR of TH cell

3. 3. MHC의 유전자 구성 b) The Ig-like region
- Consist of 2 domain of  chain and β2 domain of β chain
- Non-polymorphic
- β2 domain interact with CD4 of T cell
c) The transmembrane and cytoplasmic regions
- Transmembrane region: 25 hydrophobic aa residue
- cytoplasmic region: short, hydrophilic tail
3. MHC의 유전자 구성
1) MHC 유전자좌의 구성
- Human: chromosome 6
- Occupies a large segment of DNA, extending about 3500 kbp
a) The MHC class I
- MHC class I: encoded by A, B, C
- A heterozygous individual expresses six different polymorphic alleles ( three from each parent) and six MHC class I molecules per cell
- Class I-like: coded by F, G, H, J and X function as an Fc receptor for IgG
b) The MHC class II
- MHC class II: coded by DP, DQ, DR
- Usually 2-3 functional β chain genes for some class II loci but usually only one  chain gene
- Individuals can express 10 to 20 different class II gene products per cell

4. 4. MHC 분자의 발현 조절
1) The constitutive expression of class I molecule is distinct from that of class II molecules
- MHC class I: all nucleated cells
- MHC class II: B cell, macrophage, dendritic cells, endothelial cells
2) Cytokines can modulate the rate of transcription of class I and class II genes
a) MHC class I
- γ-interferon (IFN-γ): increase the level expression of class I molecules
- IFN-, IFN-β and TNF (tumor necrosis factor): also increase class I molecule expression
b) MHC class II
- macrophage: IFN-γ increase class II expression but IFN-, IFN-β and IL-10 decrease class II expression
- Endothelial cell: IFN-γ increase class II expression
- B cells and lymphoid dendritic cells: constitutively express class II molecule