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Major Histocompatibility Complex (MHC) bind peptide fragments from pathogens, and present them on the cell surface to be detected by T cells . There are 2 types of MHC Molecule: Class 1 MHC and Class 2 MHC:
MHC Class 1
- MHC Class 1 molecules are expressed in all nucleated cells.
- These are involved in the presentation of endogenous antigens (those found intracellularly).
- Presentation of MHC class I molecules: antigen is synthesised in the cytoplasm., the foreign protein is cleaved into peptide via proteasome, the peptide is then transported into the endoplasmic reticulum via the TAP transporter where it then binds to MHC class I, the complex made of MHC class I molecules and peptide is transported to cell surface.
- Presentation of these endogenous antigens is recognised by Cytotoxic T cells that destroy the antigen via a mechanism involving the use of Granzyme and Perfornin.
- MHC class 1 molecules have 3 alpha subunits and 1 beta microglobin subunit. Both alpha 1 and 2 form the antigen presenting region of the molecule .
- MHC class 1 has only one transmembrane domain that anchors it into the cell membrane.
- MHC Class 1 proteins in humans come in three major types: HLA-A; HLA-B and HLA-C, with HLA standing for human-leukocyte-associated.
MHC Class 2
- MHC Class 2 are expressed in professional antigen presenting cells such as macrophages and B Cells.
- They present exogenous antigens (those made outside the cell). They bind peptides 18-20 amino acids long.
- Presentation of MHC class II molecules: antigen is endocytosed into a vesicle, protein within this vesicle is cleaved into peptides by an acidic protease, MHC Class II is engulfed into a vesicle, and has an invariant chain bound in peptide binding groove, this is broken down leaving CLIP. CLIP is removed by HLA-DM, and this allows the peptide in the other vesicle to bind, once it has bound.
- Unlike MHC Class 1 receptors, these molecules have two alpha and two beta subunits, with transmembrane spanning regions from alpha-2 and beta-2. The alpha-1 and beta-1 subunits form an antigen presenting site.
- In humans the MHC Class II protein has three forms: HLA-DR, HLA-DP and HLA-DQ
- ↑ Murphy K. Weaver C. Janeway's Immunobiology. 9th Edition. Garland Science, Taylor and Francis Group. New York and London. 2016.
- ↑ Mayer G, Nyland J. Major Histocompatibility Complex(MHC)and T-cell receptors - role in immune response. 2017 [cited 19.10.17]. Available from: http://www.microbiologybook.org/bowers/mhc.htm
- ↑ Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P. Molecular Biology of the Cell. 6th Ed, Abingdon: Garland Science, Taylor and; Francis Group. 2015.