Major Histocompatibility Complex (MHC) Genes

Jerzy K Kulski, Tokai University School of MedicineKanagawa, Japan andCBBC Information Technology, Murdoch University, Murdoch, Australia
Hidetoshi Inoko, Tokai University School of Medicine, Kanagawa, Japan

Published online: January 2006

DOI: 10.1038/npg.els.0005900

MHC genes are located within the human major histocompatibility complex (MHC) and code for different members of the class I and the class II human leukocyte antigen (HLA) families. The HLA class I and class II molecules are polymorphic cell membrane-bound glycoproteins and, as part of the immunosurveillance system, they regulate the immune response by presenting fragmented proteins (peptides) to circulating cytotoxic and helper T lymphocytes respectively.

Keywords: MHC; HLA; class I; class II; duplication; polymorphism

Figure 1. Genomic map of the location of the HLA class I and class II genes and pseudogenes within the ‘virtual MHC’. The open and shaded boxes represent pseudogenes and coding genes respectively. The MHC class I, II and III regions, and the HLA alpha, beta and kappa evolutionary blocks within the class I region are labeled and indicated by the double arrows. IVS1 is the intervening sequence (247 kb) between the alpha and kappa blocks, IVS2 is the intervening sequence (737 kb) between the kappa and beta blocks and IVS3 is the intervening sequence (215 kb) between the class II and III regions. The approximate lengths of the class I, II and III regions, and the class I duplication blocks in the ‘virtual MHC’ are given in parentheses. The differences in gene content in the class II DR region are indicated. This is an abbreviated map and many of the non-HLA genes found within the MHC or between the HLA genes are not shown here. The extended class II region and the differences in gene content in the C4 region of class III are not included in this figure. (See The MHC Sequencing Consortium (1999) for further details.)
Figure 2. The structure of the MHC class I and class II proteins.
Figure 3. Schematic representation of the MHC class I and class II gene promoters, regulatory elements and transcription factors. The conserved regulatory elements are indicated as a series of boxes and circles along the horizontal lines representing the class I promoter region (top) and the class II promoter region (bottom). The bent arrow at the end of the horizontal line represents the position of the transcription initiation site and the direction of transcription. The DNA-binding factors (boxed) and the MHC class I and class II regulatory elements with which they interact are indicated by the vertical arrows. Non-DNA-binding regulatory cofactors, such as CIITA, which bind to the DNA-binding regulators in cooperative interactions are not shown. (Modified from van den Elsen et al. (1998).)
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 References
    Bahram S (2000) MIC genes: from genetics to biology. Advances in Immunology 76: 1–60.
    Beck S and Trowsdale J (1999) Sequence organisation of the class II region of the human MHC. Immunological Reviews 167: 201–210.
    Bjorkman PJ, Saper MA, Samraoui B, et al. (1987) Structure of human class I histocompatibility antigen, HLA-A2. Nature 329: 506–512.
    Brown JH, Jardetzky TS, Gorga JC, et al. (1993) Three dimensional structure of the human class II histocompatibility antigen, HLA-DR1. Nature 364: 33–39.
    book Charron D (ed.) (1997) "HLA: Genetic Diversity of HLA. Functional and Medical Implication". Proceedings of the 12th International Histocompatibility Workshop and Conference, vols 1 and 2. Paris: EDK.
    van den Elsen, Gobin SJP, van Eggermond MCJA and Peijnenburg A (1998) Regulation of MHC class I and II gene transcription: differences and similarities. Immunogenetics 48: 208–221.
    Gobin SJ and van den Elsen PJ (2000) Transcriptional regulation of the MHC class Ib genes HLA-E, HLA-F, and HLA-G. Human Immunology 61: 1102–1107.
    Gussow D, Rein RS, Meijer I, et al. (1987) Isolation, expression, and the primary structure of HLA-Cw2 genes: evolutionary aspects. Immunogenetics 25: 313–322.
    van Ham M, van Lith M, Griekspoor A and Neefjes J (2000) What to do with HLA-DO. Immunogenetics 51: 765–770.
    Hill AVS (1998) The immunogenetics of human infectious diseases. Annual Reviews in Immunology 16: 593–617.
    Koller BH, Geraghty DE, Shimizu Y, DeMars R and Orr HT (1988) HLA-E. A novel HLA class I gene expressed in resting T lymphocytes. Journal of Immunology 141: 897–904.
    Kulski JK, Gaudieri S and Dawkins RL (2000) Using Alu J elements as molecular clocks to trace the evolutionary relationships between duplicated HLA class I segments. Journal of Molecular Evolution 50: 510–519.
    Kulski JK, Gaudieri S, Martin A and Dawkins RL (1999) Co-evolution of PERB11 (MIC) and HLA class I genes with HERV-16 and retroelements by extended genomic duplication. Journal of Molecular Evolution 49: 84–97.
    Magner WJ and Tomasi TB (2000) Review. Chromatin–immune connections: regulation of MHC and other genes. Journal of Reproductive Immunology 48: 1–15.
    McKiernan SM, Hagan R, Curry M, et al. (2000) The MHC is a major determinant of viral status, but not fibrotic stage, in individuals infected with hepatitis C. Gastroenterology 118: 1124–1130.
    Radley E, Alderton RP, Kelly A, Trowsdale J and Beck S (1994) Genomic organisation of HLA-DMA and HLA-DMB. Comparison of the gene organisation of all six class II families in the human major histocompatibility complex. Journal of Biological Chemistry 269: 18834–18838.
    Roche PA, Marks MS and Cresswell P (1991) Formation of a nine-subunit complex by HLA class II glycoproteins and invariant chain. Nature 354: 392–394.
    Shiina T, Tamiya G, Oka A, et al. (1999) Molecular dynamics of MHC genes is unraveled by sequence analysis of the 1,796,938 bp HLA class I region. Proceedings of the National Academy of Sciences of the United States of America 96: 13282–13287.
    The MHC Sequencing Consortium (1999) Complete sequence and gene map of a human major histocompatibility complex. Nature 401: 921–923.
    book Tiwari JL and Terasaki PI (1985) "HLA antigens associated with diseases". Anonymous HLA and Disease Associations, pp. 42–48. New York, NY: Springer.
    Wei X and Orr HT (1990) Differential expression of HLA-E, HLA-F and HLA-G transcripts in human tissue. Human Immunology 29: 131–136.
 Further Reading
    book Browning M and McMichael A (eds.) (1996) HLA and MHC. Genes, Molecules and Function Oxford, UK: BIOS Scientific Publishers.
    Dawkins RL, Leelayuwat C, Gaudieri S, et al. (1999) Genomics of the major histocompatibility complex: haplotypes, retroviruses and disease. Immunological Reviews 167: 275–304.
    van den Elsen, Peijnenburg A, van Eggermond MCJA and Gobin SJP (1998) Shared regulatory elements in the promoters of MHC class I and class II genes. Immunology Today 19: 308–312.
    book Klein J (1986) Natural History of the Major Histocompatibility Complex New York, NY: Wiley.
    book Kulski JK, Gaudieri S and Dawkins RL (2000) "Transposable elements and the metamerismatic evolution of the HLA class I region". Kasahara M (ed.) The Major Histocompatibility Complex: Evolution, Structure, and Function, pp. 158–177. Tokyo: Springer
    Nepom GT and Erlich H (1991) MHC class-II molecules and autoimmunity. Annual Reviews in Immunology 9: 493–525.
    Pieters J (2000) MHC class II-restricted antigen processing and presentation. Advances in Immunology 75: 159–208.
    Salter-Cid L and Flajnik MF (1995) Evolution and developmental regulation of the major histocompatibility complex. Critical Reviews in Immunology 15: 31–75.
    Shiina T, Tamiya G, Oka A, Takishima N and Inoko H (1999) Genome sequencing analysis of the 1.8 Mb entire human MHC class I region. Immunological Reviews 167: 193–199.
 Web Links
    ePath Australasian and South East Asian, Tissue Typing Association (ASEATTA). HLA tissue typing education primer http://www.aseatta.org.au/HLAintro.htm
    ePath European Bioinformatics Institute. HLA genes and number of alleles http://www.ebi.ac.uk/imgt/hla/stats
    ePath European Bioinformatics Institute. IMGT/HLA sequence database homepage http://www.ebi.ac.uk/imgt/hla/loci.html
    ePath Major Histocompatibility Complex. MHC reviews by M Tevfik Dorak http://dorakmt.tripod.com/mhc/mhc.html
    ePath http://mhc-x.u-strasbg.fr/ MHC-X. MHC class I related genes
    ePath RasMol gallery. MHC class I and class II three-dimensional structures http://www.umass.edu/microbio/rasmol/galmz.htm#abag
    ePath The Stern Laboratory. MHC class I and class II three-dimensional structures http://web.mit.edu/user/s/t/stern/www/index.html
    ePath The Stern Laboratory. MHC class I and class II three-dimensional structures http://web.mit.edu/user/s/t/stern/www/mhctools.htm
    ePath The Wellcome Trust Sanger Institute. Complete human MHC sequence http://www.sanger.ac.uk/HGP/Chr6/MHC.shtml
    ePath W H Freeman. MHC lectures: chapter 9: Major histocompatibility complex http://www.whfreeman.com/Immunology/CH09/kuby09.htm
    ePath W H Freeman. MHC class I and class II three-dimensional structures http://www.whfreeman.com/Immunology/CH09/class2.htm

Related Sub-Topics:

Acquired (Adaptive) Immunity | Major Histocompatibility Complex | Membrane Proteins | Protein Structure | Translation and Protein synthesis | Protein Folding, Evolution and Degradation | Molecular Genetics of Common and Complex Disease | Gene and Genome Structure and Organisation | Inter-Individual Variation and Polymorphism
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Article Title: Major Histocompatibility Complex (MHC) Genes
 
How to Cite close
Kulski, Jerzy K, and Inoko, Hidetoshi(Jan 2006) Major Histocompatibility Complex (MHC) Genes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005900]