| First Author | Reizis B | Year | 1997 |
| Journal | Eur J Immunol | Volume | 27 |
| Issue | 10 | Pages | 2478-83 |
| PubMed ID | 9368599 | Mgi Jnum | J:44144 |
| Mgi Id | MGI:1099396 | Doi | 10.1002/eji.1830271003 |
| Citation | Reizis B, et al. (1997) Biochemical characterization of the human diabetes-associated HLA-DQ8 allelic product: similarity to the major histocompatibility complex class II I-A(g)7 protein of non-obese diabetic mice. Eur J Immunol 27(10):2478-83 |
| abstractText | The human HLA-DQ8 (A1*0301/B1*0302) allelic product manifests a strong association with insulin-dependent diabetes mellitus (IDDM). Previous biochemical studies of the major histocompatibility complex (MHC) class II I-A(g)7 protein of IDDM-prone non-obese diabetic mice produced controversial results. To better define the biochemical properties of IDDM-associated MHC class II molecules, we analyzed DQ8 proteins, in comparison to other DQ allelic products, by partially denaturing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). We now report that DQ8 proteins have a normal peptide occupancy and lifespan in cells. Similar to I-A(g)7, DQ8 proteins formed only a minor fraction of SDS-stable complexes with peptides. Although this phenotype was not unique to DQ8, some DQ allelic products such as IDDM-protective DQ6 proteins were SDS resistant. The DQ9 allelic product, differing from DQ8 only at position (P) beta 57, was SDS stable, suggesting that non-Asp residues at beta 57 might decrease the SDS stability of DQ proteins. We identified a single peptide which specifically induced an SDS-stable conformation in DQ8 as well as in I-A(g)7 molecules. The residues at anchor P1 in this peptide were found to influence the SDS stability of both molecules. Together with our previous observation of similar binding motifs of I-A(g)7 and DQ8, these results demonstrate an overall biochemical similarity of mouse and human diabetes-associated MHC class II molecules. This similarity might contribute to a common immunological mechanism of IDDM in both species. |
