Major Histocompatibility Complex Molecules - Essay Example

?Major Histocompatibility Complex (MHC) Molecules In most vertebrates, cell surfaces contain molecules that for certain types of proteins, of which the presence of proteins coding for peptides of foreign or pathogenic origin trigger immune responses from leukocytes or the white blood cells. These cell membrane molecules are called major histocompatibility complex (MHC) molecules, also known as human leukocyte antigens (HLA) molecules, known to have high polymorphism due to the properties of the polypeptide chains that make up these molecules (Gershwin & Shoenfield 2000; Hughes & Nei 1989). MHC molecules comprise of three classes, two of which are directly involved in the processing of antigen molecules and the release of immune cells (Morrow, et al. 2012). The first class, MHC Class I molecules are mostly involved in the acquisition of protein molecules outside of the cell (exocytic), while the second class, MHC Class II molecules are mostly involved in the processes of acquiring proteins from endocytic processes engulfed by lysosomes inside the cell (Williams 2012). Both classes of MHC’s can be found on the surfaces of cells, however the kinds of cells that they are present in differ in each class due to the differences in polypeptide compositions and corresponding functions. MHC Class I molecules are much more abundant, as these proteins are found on each nucleated cell in order to represent the proteins that originated inside the cell for T cells to detect (Coico & Sunshine 2009). The exocytic nature of MHC Class I cells are due to the single MHC polypeptide chain (?-polypeptide chain) associated with a non-MHC polypeptide called the ?2-polypeptide chain (Karp 2009). High levels of polymorphism of the peptide binding regions in the ?-polypeptide chain can be traced to the different sequences of the amino acid, making it easy for the molecule to adjust the binding region to accommodate a wide variety of peptides (Grusby, et al. 1993; Male, et al. 2006). This high level of polymorphism also entails that the binding regions can accommodate and hold a wide variety of peptides due to wider pockets, thus allowing the entry of peptides even with various kinds of orientations (Morrow, et al. 2012). The attachment of the MHC Class I molecule on the cell, the helical formation of the long ?-polypeptide chain, the peptide binding site (or alloantigenic site) consisting of ?-1 and ?-2 polypeptide chains, and the attachment of the non-polymorphic ?2-polypeptide are shown in Figure 1. On the other hand, MHC Class II molecules are mostly present only on antigen-presenting cells (APC’s) such as white blood cells and T cells, since these molecules mostly interact with cells that contain extracellular proteins rooting from the autophagy of foreign peptides (Male, et al. 2006). While having similarities with the MHC Class I molecules having ?- and ?-polypeptide chains, in contrast with the Class I molecules having an asymmetrical shape due to the longer ?-chain regions and single ?2-chain, the ?- and ?-chains in Class II molecules are structurally similar which creates a near-symmetrical molecule, of which the ?-1 and ?-1 chains are involved in the formation of the peptide binding region (Williams 2012). Also, in contrast to Class I molecules that mostly interact with peptides originating from either the cell or outside the cell and thus have binding regions with higher polymorphism, Class II molecules bind with peptides originating from autophagy degradation and other products of lysosomal proteolysis assimilated into the cell, which only entail the formation of a much more open-ended and shallower peptide binding region (Gershwin & Shoenfield 2000; Morrow, et al. 2012; Schmid, et al. 2007). Due to this, there is a greater likelihood that very long peptides would not easily attach to the binding site, and either long polypeptides could only fit loosely in the grooves or the relatively shorter ones would have better chances of binding in the site (Morrow, et al. 2012). Figure 2 shows the attachment of the MHC Class II molecule on the cell membrane, the nearly-symmetrical appearance of the ?-polypeptide and ?2-polypeptide chains due to the helical folding of the two chains, and the peptide binding site formed by the ?-1 and ?-1 chains. Figure 1. Major Histocompatibility Complex Class I (MHC Class I) diagram shows the long ?-chain, with ?-1 and ?-2 consisting the peptide binding region (alloantigenic site), the ?-3 chain attached to the cell membrane surface, and the non-polymorphic non-MHC ?2-polypeptide chain (Mayer & Nyland 2010). Figure 2. Major Histocompatibility Complex Class II (MHC Class II) diagram showing the ?- and ?-polypeptide chains with near symmetry, with the ?-1 and ?-1 chains forming the peptide binding site of the molecule (Mayer & Nyland 2010). The high levels of polymorphism of MHC molecules can be attributed to the variability of peptide binding regions, arising from the differences in the amino acid sequences of the peptide chains (Coico & Sunshine 2009). However, what set the two classes of MHC molecules apart would be the parts of their respective domains, and in turn distinguishes the function of one class from the other. The MHC Class I molecules mostly consist of a long ?-chain, two parts of which contain the peptide binding regions of the molecule, and the high variability of this region allows for the binding of many kinds and lengths of peptides (Morrow, et al. 2012). This is relevant to the function and location of the Class I molecules since these are found abundantly on various kinds of nucleated cells, sending signals for the lysing of damaged or dying cells. On the other hand, Class II molecules which are found mostly on immune cells such as leukocytes have both ?- and ?-polypeptide chains that function together to create the peptide binding region of the molecule (Williams 2012). While not as high-variable as the Class I molecule due to a less stricter and smaller binding site, the binding regions of Class II molecules are variable enough to accommodate proteins with enough affinity to be carried onto the cell’s surface (Morrow, et al. 2012). This is relevant to the function of the molecules since Class II molecules interact with T cells in subduing potential harm, and by discounting proteins found in the cytosol, there would be greater focus on the autophagy of cells that contain extracellular proteins, thereby preventing the invasion of pathogens in the body (Schmid, et al. 2007). It can be deduced that the functions of the MHC molecule is dependent on the kinds of polypeptide chains as well as the levels of polymorphism of the peptide binding sites, and these differences are shown through the structural differences of the molecules’ peptide chains. Bibliography Coico, R. & Sunshine, G., 2009. Immunology: A short course. 6th ed. Hoboken, NJ: John Wiley & Sons, Inc. Gershwin, M. & Shoenfield, Y., 2000. Cancer and Autoimmunity. Amsterdam: Elsevier Science B.V.. Grusby, M. et al., 1993. Mice lacking major histocompatibility complex class I and class II molecules. Proceedings of the National Academy of Sciences, USA, Volume 90, pp. 3913-3917. Hughes, A. & Nei, M., 1989. Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proceedings of the National Academy of Sciences, USA, Volume 86, pp. 958-962. Karp, G., 2009. Cell and Molecular Biology: Concepts and Experiments. 6th ed. Hoboken, NJ: John Wiley & Sons, Inc.. Male, D., Brostoff, J., Roth, D. & Roitt, I., 2006. Immunology. 7th ed. Philadephia, PA: Elsevier Health Sciences. Mayer, G. & Nyland, J., 2010. Major Histocompatibility Complex. [Online] Available at: http://pathmicro.med.sc.edu/bowers/mhc.htm [Accessed 26 July 2013]. Morrow, W., Sheikh, N., Schmidt, C. & Davies, D., 2012. Vaccinology: Principles and Practice. West Sussex: John Wiley & Sons, Ltd.. Schmid, D., Pypaert, M. & Munz, C., 2007. MHC class II antigen loading compartments continuously receive input from autophagosomes. Immunity, 26(1), pp. 79-92. Williams, A. E., 2012. Immunology: Mucosal and Body Surface Defences. West Sussex: John Wiley & Sons, Ltd.. Read More