MHC genes the immune response and disease

The MHC lies on the short arm of chromosome 6 and encodes a diverse range of proteins, notably antigen presenting molecules by class I and II region genes (Fig. 12.1) (Horton et al. 2004). The MHC class I supercluster includes three classical class I genes (HLA-A, -B, and -C) whose products are involved in presentation of antigen to CD8+ T cells; four non-classical class I genes (HLA-E, -F, -G, and HFE); and 12 pseudogenes and class I-like genes such as MICA and MICB. The class II cluster includes the classical genes HLA-DP, -DQ, and -DR that encode a and P chains expressed as heterodimers on the cell surface and are responsible for the presentation of antigens to CD4+ T cells. The class I and II gene clusters span a 3.6 Mb region, with the sequence between the two clusters denoted the class III region. The class III region has the highest gene density of anywhere in the genome with 61 expressed genes within 900 kb (Xie et al. 2003).

The MHC is now generally considered to also include flanking regions beyond class I and II such that the extended MHC spans 7.6 Mb of the genome. This demarcation arose through analysis of the patterns of linkage

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