MHC locus

Defects in MHC Class II molecules, while exposing affected subjects to a variety of infections, do not result in the severe immunodeficiency seen in patients with SCID. In contrast to mutations affecting MHC Class II molecules, defects in MHC Class I molecules are rare. Mutations affecting MHC Class I molecules are directed to genes on chromosome 6 at the MHC locus that code for peptide-transporter proteins (122). The function of these transporter proteins is to transport the peptide antigens so that a complex with the a chain of MHC Class I molecules and p 2-microglobulin is formed and transported to the surface of the cell. 

DHEAS Dehydroepiandrosterone sulfate HLA Major histocompatibility (MHC) locus... 

An important question concerns the effect of the minor shift on the isochore pattern. This problem has been explored on all syntenic regions shared by human and mouse, that were large enough to comprise more than one isochore. The results of this investigation (Pavli-cek et al., 2002b) indicate that the human isochore pattern is still recognizable in the mouse chromosomes after the minor shift. This will be illustrated here by considering the major histocompatibility (MHC) locus. 

The recent sequencing of the mouse MHC locus oflers a first opportunity to compare a... 

Fukagawa T., Sugaya K., Matsumoto K., Okumura K., Ando A., Inoko H., Ikemura T. (1995) A boundary of long-range G + C% mosaic domains in the human MHC locus pseudoautosomal boundary-like sequence exists near the boundary. Genomics 25 184-191. 

ANAb Anti-nuclear antibodies ANCA Anti-neutrophil cytoplasmic auto antibodies cANCA Cytoplasmic ANCA pANCA Perinuclear ANCA AND Anaphylactic degranulation ANF Atrial natriuretic factor ANP Atrial natriuretic peptide Anti-I-A, Anti-I-E Antibody against class II MHC molecule encoded by I-A locus, I-E locus, anti-lg Antibody against an immunoglobulin... 

Type 1 diabetes affects approximately 1 in 200 Americans, with a sibling recurrence risk of about 6%. It is an example of an autoimmune disease (see Immunology Lecture Notes), in which self-reactive T cells infiltrate the pancreas to destroy insulin-produdng islet cells. Mutations in the class II major histocompatibility locus (MHC) region are estimated to contribute about one third of the risk of developing type 1 diabetes. Mutations in or near the insulin gene itself are responsible for another 10-15% of the risk. 

Until now the reasons for why allergies affect only some patients and not others are not evident. It is also not known what causes an allergy to a specific allergen. A positive correlation between the rate of occurrence of major histocompatibility complex (MHC) genes (especially DR locus) and the frequency of allergies to specific allergens is being verified. 

Fig. 14.3 Tumor necrosis factor (TNF) locus with some of the polymorphic sites known within the TNF locus. C2, C4, complement C2, C4 Ch, chromosome HLA, human leukocyte antigen HSP, heat shock protein LTA, lymphotoxin A LTB, lymphotoxin B MHC, major histocompatibility complex. (Reproduced from ref 74 by permission of Future Medicine Ltd.)...

The MHC region is divided into three snbgronps, class I, class II and class IE. Class El has a function very different from that of class I and class II (Table 15.4), but since it has a locus between the other two (on chromosome 6 in humans), the three classes are frequently discussed together MHC class III encodes for immune components such as complement (C2, C4, factor B), as well as cytokines (e.g. tumour necrosis factor (TNF)). 

Only some autoimmune diseases are almost exclusively associated with MHC class I alleles of the HLA-A, HLA-B, or HLA-C locus. One of the strongest MHC disease associations is between HLA-B27 and the spondyloarthropathies, especially ankylosing spondylitis and reactive arthritis. B27 molecules seem to play a direct role in disease pathogenesis (David, 1997). Although the exact mechanism is unknown, it has been shown that HLA-B27 is capable of presenting potentially arthritogenic peptides to cytotoxic T cells (Bowness, 2002). 

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