A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus.
Open Access
- 1 April 1990
- journal article
- research article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 85 (4) , 1315-1319
- https://doi.org/10.1172/jci114569
Abstract
Family and population studies indicate that predisposition to insulin-dependent (type I) diabetes mellitus (IDDM) is polygenic. It has been shown that the absence of the aspartic acid in position 57 (Asp57) of the DQ beta chain is positively correlated to IDDM. However, Asp57-negative haplotypes do not always confer susceptibility and conversely, some Asp57-positive haplotypes seem to be disease associated. It has been suggested that other HLA class II sequences, probably belonging to the HLA DQA1 gene, confer susceptibility to IDDM. This report, based on extensive oligonucleotide dot blot hybridization of PCR-amplified DQA1 and DQB1 genes, reinforces the importance of the Asp57-negative DQ beta chain, but also introduces the possibility that a DQ alpha chain bearing an arginine in position 52 (Arg52) confers susceptibility to IDDM. A molecular model of susceptibility to IDDM is proposed. This model strongly suggests that the disease susceptibility correlates quantitatively with the expression at the cell surface of a heterodimer, composed of a DQ alpha-chain bearing an Arg52 and a DQ beta chain lacking an Asp57. In view of the respective positions of the two residues and their charge, we might anticipate that both residues DQ beta Asp57 and DQ alpha Arg52 are critical for modulation of susceptibility, presumably via viral-antigenic peptide and/or autoantigen presentation.Keywords
This publication has 20 references indexed in Scilit:
- Oligonucleotide probes for HLA-DQA and DQB genes define susceptibility to Type 1 (insulin-dependent) diabetes mellitusDiabetologia, 1988
- A hypothetical model of the foreign antigen binding site of Class II histocompatibility moleculesNature, 1988
- HLA-DQβ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitusNature, 1987
- The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigensNature, 1987
- Structure of the human class I histocompatibility antigen, HLA-A2Nature, 1987
- Structural characteristics of an antigen required for its interaction with Ia and recognition by T cellsNature, 1987
- Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin-dependent diabetes mellitus with HLA-DQ.Journal of Clinical Investigation, 1987
- Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probesNature, 1986
- Only one DQ-beta restriction fragment pattern of each DR specificity is associated with insulin-dependent diabetes.The Journal of Immunology, 1986
- The genetic susceptibility to type 1 (insulin-dependent) diabetes: Analysis of the HLA-DR associationDiabetologia, 1983