MHC class III
MHC class IIIis a group of proteins belonging the class ofmajor histocompatibility complex(MHC). Unlike other MHC types such asMHC class IandMHC class II,of which their structure and functions inimmune responseare well defined, MHC class III are poorly defined structurally and functionally. They are not involved inantigenbinding (the process calledantigen presentation,a classic function of MHC proteins). Only few of them are actually involved in immunity while many aresignalling moleculesin other cell communications. They are mainly known from their genes because their gene cluster is present between those ofclass Iandclass II.[1]The gene cluster was discovered when genes (specifically those of complement componentsC2,C4,andfactor B) were found in between class I and class II genes on the short (p) arm ofhuman chromosome 6.It was later found that it contains many genes for different signaling molecules such astumour necrosis factors(TNFs) andheat shock proteins.More than 60 MHC class III genes are described, which is about 28% of the total MHC genes (224).[2]The region previously considered within MHC class III gene cluster that contains genes for TNFs is now known as MHC class IV[3]or inflammatory region.[4]
In contrast to other MHC proteins, MHC class III proteins are produced by liver cells (hepatocytes) and special white blood cells (macrophages), among others.
Gene structure
[edit]MHC class III genes are located on chromosome 6 (6p21.3) in humans. It covers 700 kb and contains 61 genes. The gene cluster is the most gene-dense region of the human genome. They are basically similar with those of other animals. The functions of many genes are yet unknown.[5]Manyretroelementssuch ashuman endogenous retrovirus(HERV) andAlu elementsare located in the cluster.[6]The region containing genesSTK19(G11)/C4/Z/CYP21/X/Y,varying in size from 142 to 214 kb, is known as the most complex gene cluster in the human genome.[7]
Diversity
[edit]MHC class III genes are similar in humans, mouse, frog (Xenopus tropicalis), andgray short-tailed opossum,but not all genes are common. For example, humanNCR3,MICandMCCD1are absent in mouse. HumanNCR3andLST1are absent in opossum.[4]However, birds (chicken and quail) have only a single gene, which codes for a complement component gene (C4).[8]In fishes, the genes are distributed in different chromosomes.[9]
References
[edit]- ^Gruen, JR; Weissman, SM (2001)."Human MHC class III and IV genes and disease associations".Frontiers in Bioscience.6(3): D960-172.doi:10.2741/A658.PMID11487469.
- ^The MHC sequencing consortium (1999). "Complete sequence and gene map of a human major histocompatibility complex".Nature.401(6756): 921–923.Bibcode:1999Natur.401..921T.doi:10.1038/44853.PMID10553908.S2CID186243515.
- ^Gruen JR, Weissman SM. Human MHC class III and IV genes and disease associations. Front Biosci. 2001 Aug 1;6:D960-72. doi: 10.2741/gruen. PMID 11487469.
- ^abDeakin, Janine E; Papenfuss, Anthony T; Belov, Katherine; Cross, Joseph GR; Coggill, Penny; Palmer, Sophie; Sims, Sarah; Speed, Terence P; Beck, Stephan; Graves, Jennifer (2006)."Evolution and comparative analysis of the MHC Class III inflammatory region".BMC Genomics.7(1): 281.doi:10.1186/1471-2164-7-281.PMC1654159.PMID17081307.
- ^Xie, T; Rowen, L; Aguado, B; Ahearn, ME; Madan, A; Qin, S; Campbell, RD; Hood, L (2003)."Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse".Genome Research.13(12): 2621–36.doi:10.1101/gr.1736803.PMC403804.PMID14656967.
- ^Dawkins, R; Leelayuwat, C; Gaudieri, S; Tay, G; Hui, J; Cattley, S; Martinez, P; Kulski, J (1999). "Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease".Immunological Reviews.167:275–304.doi:10.1111/j.1600-065X.1999.tb01399.x.PMID10319268.S2CID9924684.
- ^Milner, CM; Campbell, RD (2001)."Genetic organization of the human MHC class III region".Frontiers in Bioscience.6(3): D914-926.doi:10.2741/A653.PMID11487476.
- ^Shiina, T; Shimizu, S; Hosomichi, K; Kohara, S; Watanabe, S; Hanzawa, K; Beck, S; Kulski, JK; Inoko, H (2004)."Comparative genomic analysis of two avian (quail and chicken) MHC regions".Journal of Immunology.172(11): 6751–63.doi:10.4049/jimmunol.172.11.6751.PMID15153492.
- ^Sambrook, JG; Figueroa, F; Beck, S (2005)."A genome-wide survey of Major Histocompatibility Complex (MHC) genes and their paralogues in zebrafish".BMC Genomics.6:152.doi:10.1186/1471-2164-6-152.PMC1309616.PMID16271140.