Specific molecular interaction between the insulin receptor and a D product of MHC class I
Verland, S.; Simonsen, M.; Gammeltoft, S.; Allen, H.; Flavell, R.A.; Olsson, L.
Journal of Immunology 143(3): 945-951
1989
ISSN/ISBN: 0022-1767 PMID: 2473115 Document Number: 331153
The density of MHC class I was determined on a murine thymoma cell line (R1), and H-2 negative variant (R1E), and R1E-derived cell lines in which H-2 expression was restored by transfection of various MHC class I genes (Db, Kb, and truncated Db) and/or a .beta.-2-microglobulin gene (beta 2-m; B2). Appreciable MHC class I expression was found on R1 cells and on the variants in which MHC class I expression was restored by transfection of Db/.beta.2-m or Kb/.beta.2-m genes. Only .apprx. 20% difference was observed between the number of Db molecules and Kb molecules on the R1E/B2/Db and on R1E/B2/Kb, respectively. However, specific insulin binding was significantly different between these lines. By using a computer assisted curve fitting program, the insulin binding data for R1 and R1E/B2/Db cell lines best fitted a two-site model (K .apprx. 6 .times. 10-9M for high-affinity sites and a 2 to 3 .times. 10-7 M for low-affinity sites), whereas all other lines only expressed one type of insulin binding site. These sites were unrelated to IGF-I and IGF-II receptors. Cross-linking of 125I-labeled insulin demonstrated specific binding of the ligand to a Mr .apprx. 130,000 dalton band in all lines. In the R1E/B2/Db cells, insulin also cross-linked to cell membrane molecules with Mr .apprx. 48,000 and .apprx. 60,000 Da, which were identified by immunprecipitation to be the H chain of MHC class I and the heavy chain of MHC class I plus .beta.-m, respectively. It is concluded that the insulin receptors in the cell membrane interact specifically with D-products of MHC class I and that class I molecules of MHC may have a crucial role in insulin recpetor expression. This may reflect a more general nonimmunologic role of MHC class I.