Major Histocompatibility Complex (MHC) Genes


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 membraneā€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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Further Reading

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.

Klein J (1986) Natural History of the Major Histocompatibility Complex New York, NY: Wiley.

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

Australasian and South East Asian, Tissue Typing Association (ASEATTA). HLA tissue typing education primer

European Bioinformatics Institute. HLA genes and number of alleles

European Bioinformatics Institute. IMGT/HLA sequence database homepage

Major Histocompatibility Complex. MHC reviews by M Tevfik Dorak

http://mhc‐x.u‐ MHC‐X. MHC class I related genes

RasMol gallery. MHC class I and class II three‐dimensional structures

The Stern Laboratory. MHC class I and class II three‐dimensional structures

The Stern Laboratory. MHC class I and class II three‐dimensional structures

The Wellcome Trust Sanger Institute. Complete human MHC sequence

W H Freeman. MHC lectures: chapter 9: Major histocompatibility complex

W H Freeman. MHC class I and class II three‐dimensional structures

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Kulski, Jerzy K, and Inoko, Hidetoshi(Jan 2006) Major Histocompatibility Complex (MHC) Genes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005900]