Transcomplementation of HLA genes in IDDM. HLA-DQ α- and β-chains produce hybrid molecules in DR3/4 heterozygotes

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Abstract

The HLA association with insulin-dependent diabetes mellitus is highest among individuals heterozygous for DR3 and DR4. To investigate potential mechanisms to account for this association, we performed two-dimensional gel-electrophoretic analysis of HLA molecules from DR3/4 heterozygous patients. These studies demonstrated hybrid molecular dimers corresponding to products of HLA-DQ genes linked to DR3 and DR4, i.e., the DQw2 and DQw3 genes, respectively. Two types of DQ molecules were found: immunoprecipitation by DQw3-specific monoclonal antibody 17.15 identified a DQw3 β-chain associating with a DQw3 α-chain and a DQw3 β-chains associating with DQw2 α-chain. The identity of α- and β-chain comprising these hybrid molecules was confirmed by HPLC peptide-map analysis. Several characteristic peptide peaks identified both DQw2 and DQw3 α-chains associated with DQW3 β-chains. The formation of such DQα(DQw2)-Dqβ(DQW3) dimers potentially contributes a direct molecular mechanism for HLA-associated contributions to disease in DR3/DR4 heterozygotes.

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APA

Nepom, B. S., Schwarz, D., Palmer, J. P., & Nepom, G. T. (1987). Transcomplementation of HLA genes in IDDM. HLA-DQ α- and β-chains produce hybrid molecules in DR3/4 heterozygotes. Diabetes, 36(1), 114–117. https://doi.org/10.2337/diab.36.1.114

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