| pubmed-article:8931340 | pubmed:abstractText | Structural modeling of the HLA-DQ molecules, a group of human histocompatibility antigens linked to autoimmune diseases and immunosuppression-based on the structure of the homologous molecule DR1, has revealed an overall shape typical of the class II histocompatibility molecules, yet with several novel features. These are unique to HLA-DQ and include: (1) an antigen-binding groove with a polymorphic first pocket and anchoring in the second and/or fifth pocket, (2) a polymorphic beta 49-56 dimerization patch, and (3) in many alleles a prominent Arg-Gly-Asp loop (beta 167-169), probably involved in cell adhesion, as it exhibits an architecture similar to identical sequences involved in such function. The alpha 2 beta 2 dimerisation domain and the CD4-binding region are nearly identical to their counterparts in the structure of HLA-DR1. The significance of the few substitutions in the CD-4 binding region remains to be evaluated. The polymorphic first antigen-binding pocket and the anchoring in the second and/or fifth pocket point to differences in antigenic fragment selection compared to HLA-DR antigens, while the polymorphism in the beta 49-56 homodimerization patch implies either ease of spontaneous or T lymphocyte receptor-induced homodimerization or difficulty in the latter. As homodimerization appears to be an obligatatory intermediate in the activation of cognate DQ-restricted T lymphocytes and DQ-bearing antigen-presenting cells, the dimerization properties of DQ allels signify the respective ease or difficulty of activation of these two cell types. The RGD loop confers cell adhesion possibilities to those DQ allels that possess it, yet its putative ligand cannot be defined at present. These features are suggestive of the probable mechanisms through which some of the unique immunological properties of the HLA-DQ molecules are effected. | lld:pubmed |
