Identification of these antigens has led to greater hla dr rheumatoid arthritis and longevity in organ transplant. Good matching of these antigens between host and donor are most critical for achieving graft survival. HLA-DR is also involved in several autoimmune conditions, disease susceptibility and disease resistance.
HLA-DR molecules are upregulated in response to signalling. DR molecule and presented to a few of a great many T-cell receptors found on T-helper cells. These cells then bind to antigens on the surface of B-cells stimulating B-cell proliferation. Increased abundance of DR ‘antigen’ on the cell surface is often in response to stimulation, and, therefore, DR is also a marker for immune stimulation. Both α and β chains are anchored in the membrane. The N-terminal domain of the mature protein forms an alpha-helix that constitutes the exposed part of the binding groove, the C-terminal cytoplasmic region interact with the other chain forming a beta-sheet under the binding groove spanning to the cell membrane. The majority of the peptide contact positions are in the first 80 residues of each chain.
HLA-DR is encoded by several loci and several ‘genes’ of different function at each locus. Unlike the other DR loci functional variation in mature DRA gene products is absent. 4 loci, however no more than 3 functional loci are present in a single individual, and no more than two on a single chromosome. Some older studies may refer to DR15 or 16 as DR2 and DQ5 and DQ6 as DQ1 therefore a haplotype DR2-DQ1 is usually referring to DR15-DQ6 but could be referring to DR16-DQ5. DR5 is used to refer to DR11 and DR12, in which case DQ3 might be used. In these instances DQ3 almost always can be interpreted as DQ7, but DR5 is most often DR11 and less frequently DR12.
Similar issues exist for DR6 versus DR13 and DR14. DR6-DQ1 can refer to either DR13-DQ6 or less frequently DR14-DQ5, but DR6-DQ3 or DR6-DQ7 generally refers to DR13-DQ7. Even older literature has more confusing designations. By looking at the change of disease association with improved testing we can see how HLA nomenclature has evolved over time. There is a high level of allelic diversity at HLA DRB1, it is second only to HLA-B locus in number of allelic variants.
These two loci are highest sequence variation rate within human genome. Much of the variation at HLA DRB1 occurs at peptide contact positions in the binding groove, as a result many of the alleles alter the way the DR binds peptide ligands and changes the repertoire each receptor can bind. This means that most of the changes are functional in nature, and therefore are under selection. HLA-DR represents an extreme example of this. A survey of X-linked loci reveals that most human loci have undergone fixation within the last 600,000 years, and diploid loci have undergone significant proportion of fixation in that period of time.
100,000 to 150,000 years ago. The HLA-DR locus represents a major exception to this observation. Based on distribution of major groupings in the human population it is possible to assert that more than a dozen major variants survived the population bottleneck. The table below provides links to subpages with information about distribution, genetic linkage and disease association for the HLA-DR serogroups.
New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans». Nomenclature for factors of the HLA System, 2004″. The myth of Eve: molecular biology and human origins». Population biology of antigen presentation by MHC class I molecules». K5 proteins: «parasites»of the endocytosis pathway». Tolstrup M, Ostergaard L, Laursen AL, et al. SIV escape from immune surveillance: focus on Nef».
HIV accessory proteins and surviving the host cell». Li L, Li HS, Pauza CD, et al. Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions». Modelling thymic HIV-1 Nef effects». Piatier-Tonneau D, Gastinel LN, Amblard F, et al.
Interaction of CD4 with HLA class II antigens and HIV gp120″. Nong Y, Kandil O, Tobin EH, et al. The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1″. HIV-gp120 can block CD4-class II MHC-mediated adhesion». Callahan KM, Fort MM, Obah EA, et al. Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor». Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain».