Structure of MHC Molecule
المؤلف:
APURBA S. SASTRY , SANDHYA BHAT
المصدر:
Essentials Of Medical Microbiology 2021
الجزء والصفحة:
3rd edition , p179-180
2025-09-04
563
Fig1. Structure of MHC molecules.
MHC Class I Molecule
It is composed of α chain (glycoprotein, 45kDa) coded by HLA class I genes and β2 microglobulin (non-glycosylated 12 kDa protein, encoded by a non MHC gene from chromosome 15).
* The α chain is folded further and organized into three extracellular globular domains—α1, α2 and α3 (each containing 90 amino acids) and a cytoplasmic tail
* The association of β2 microglobulin with α chain is necessary for the expression of MHC I molecules on to the cell surface. In Daudi cells (a type of human B cell tumor cell which are not able to produce β2 microglobulin), it is observed that they synthesize MHC-I but do not express them on cell surface.
Role of MHC Class I Molecules
* The antigen peptide binding groove of class I MHC molecule (i.e. the site, where the antigen peptide binds) is formed by the cleft between α1 and α2 domains
* The α3 domain binds to CD8 molecule present on cytotoxic T cells during antigen presentation.
MHC Class II Molecule
It comprises of one α chain (33 kDa) and one β chain (28 kDa). The α and β chains in turn consist of two domains each—(1) α1 and α2 and (2) β1 and β2, respectively and cytoplasmic tails.
* The antigen peptide binding groove is formed by the cleft between α1 and β1 domains
* The β2 domain interacts with CD4 molecule of helper T cells during antigen presentation.
Differences between MHC class I and II molecules are described in Table 1.
Table1. Differences between MHC class I and MHC class II molecules.
Regulation of MHC Expression
There are several regulatory mechanisms that control the expression of MHC genes in different cell types.
* Transcription factors: MHC genes have promoter sequences at their 5’ end which are regulated by certain transcription factors such as CIITA, and RFX (both bind to MHC II promoter genes and increase their transcription). Defects in CIITA, and RFX cause one of the form of Bare lymphocyte syndrome
* Cytokines also influence MHC expression
- IFN-γ activates both MHC-I and II promoter genes
- IL-4 increases expression of class II MHC molecules on resting B cells.
* Corticosteroid and prostaglandins decrease the expression of MHC II molecules
* In many viral infections, the viral antigens inhibit various components of MHC-I (e.g. adenovirus proteins inhibit TAP, cytomegalovirus proteins inhibit β2 microglobulin). As a result, MHC-I expression is suppressed.
MHC and Disease Susceptibility
Many HLA alleles have been associated with increased susceptibility to certain diseases (Table 2). The relative risk of occurrence of the disease in presence of the identified allele varies. For example, HLA B27 is strongly associated with ankylosing spondylitis (90 times higher risk than those not expressing HLA B 27).
Table2. Diseases associated with certain HLA alleles.
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