title: Recognition of human insulin in the context of HLA-DRB1*0406 products by T cells of insulin autoimmune syndrome patients and healthy donors.
abstract: Our recent study indicated that all the insulin autoimmune syndrome (IAS) patients had specific HLA class II alleles, the DRB1*0406, DQA1*0301, and DQB1*0302, which allowed T cells to proliferate when autologous APC were exposed to human insulin. The study implied that gene products of DRB1*0406, DQA1*0301, and/or DQB1*0302 may be involved in the presentation of human insulin to T cells. We therefore examined T cell response of healthy donors with different HLA phenotypes to human insulin using an autologous MLR system. The T cells from not only IAS patients but also healthy donors were able to proliferate after exposure of human insulin to autologous APC with DRB1*0406, DQA1*0301, and DQB1*0302 products. The class II molecules are considered to be involved in the recognition of human insulin by T cells. The proliferative response of T cells was completely blocked by anti-HLA-DR mAb and not by anti-HLA-DQ mAb or other mAb. Furthermore, human insulin-specific CD4-positive T cell clones were established from blast cells in autologous MLR of PBMC from two healthy donors with DRB1*0406 in the presence of human insulin. Using DRB1*0406-transfected L cells as APC, we confirmed that these T cells clones recognize human insulin in the context of gene products of DRB1*0406. These results provide the first evidence that HLA-DRB1*0406 products act as the dominant restriction element for the presentation of human insulin to T cells, and suggest that this particular class II gene, HLA-DRB1*0406, contributes to the development of IAS.
authors.affiliation: Department of Transfusion Medicine and Immunohematology, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Nieda
authors.forename: Y
authors.initials: Y
authors.lastname: Uchigata
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
authors.forename: S
authors.initials: S
authors.lastname: Kuwata
authors.forename: F
authors.initials: F
authors.lastname: Obata
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
authors.forename: Y
authors.initials: Y
authors.lastname: Hirata
authors.forename: Y
authors.initials: Y
authors.lastname: Omori
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells; D006684:HLA-DR Antigens / Q000502:physiology*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000276:immunology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D007328:Insulin