The goal of this proposal is to test, in vitro, the effect of the adenoviral E1a gene region on expression of the human MHC class II HLADQB1-0302 diabetes susceptibility gene. The rationale is that certain viral infections that are known to affect MHC class I and class II expression could influence the expression of diabetes susceptibility and resistance genes as well. Adenovirus is a good candidate, since many of its genes located in the E1 and E3 regions have been described to influence MHC expression. In detail, the investigators wish to address the following questions: - Is there an interaction by virally encoded transcriptional activators (adeno E1a) and specific HLA-DQB1 transcription factors, such as YY1, that is relatively selectively present in 0302 positive individuals, but, for example, not in individuals that are 0301 positive (a DQB1 allele that is not associated with insulin dependent diabetes mellitus (IDDM))? - What is the impact of the E1a transcriptional activators on the tissue specific expression of the DQB1 allele? - What are the functional consequences of the influence of adenoviral E1a expression and resulting modulation of DQB1 expression on T-cell activation in vitro?
