Polymorphic structural features of modelled HLA-DQ molecules segregate according to susceptibility or resistance to IDDM

Diabetologia
J Routsias, G K Papadopoulos

Abstract

The structural features of HLA-DQ alleles which are susceptible and resistant to insulin-dependent diabetes mellitus (IDDM) have been examined using a model of their three-dimensional structure obtained by energy minimisation, based on the published structure of HLA-DR1. The model shows DQ molecules to have an overall shape nearly identical to that of DR molecules, but with significant differences in the fine structure: 1) the antigen-binding groove of DQ molecules has a polymorphic first pocket; this pocket can be either amphiphilic or hydrophilic, 2) The beta 49-56 dimerisation domain of DQ is polymorphic: hydrophobic, or amphiphilic, or hydrophilic and positively charged, leading to spontaneous or T-cell receptor-induced homodimer formation, or T-cell receptor-induced homodimer formation, or difficulty of the formation of such dimers, respectively; 3) a prominent Arg-Gly-Asp loop is formed by some DQ alleles (beta 167-169) and probably functions in cell adhesion. There are also small differences in the residues and sequences implicated in CD4 binding (mostly in DQ beta 134-148) but the significance of these differences cannot be evaluated at present. All seven DQ alleles which confer susceptibility to IDDM possess a hydrophi...Continue Reading

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Citations

Mar 26, 1998·International Journal of Biological Macromolecules·G K PapadopoulosE Eliopoulos
Jun 26, 1998·Immunology Today·G K Papadopoulos
Nov 30, 2006·Arthritis and Rheumatism·Gulnara MamyrovaUNKNOWN Childhood Myositis Heterogeneity Collaborative Study Group
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·L S ArnesonA J Sant
Dec 10, 1999·Diabetes/metabolism Research and Reviews·C S Bartsocas
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ruth A EttingerWilliam W Kwok

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