Insulin B chain functions as an effective competitor of antigen presentation via peptide homologies present in the thymus.
The B chain of mammalian insulins contains appropriately spaced amino acids that predict recognition by T cells. However, all T cell clones from an HLA-DR1, Dw6 diabetic donor recognize epitopes associated with the A chain, and the B chain was found to inhibit these responses. Effective intramolecular competition at the level of the APC, not a direct effect on the T cell, is responsible for the inhibition. Insulin B chain contains two clusters of amino acid homology with the TCR beta chain and B chain peptides lacking these clusters do not compete for antigen presentation. A hole in the repertoire for T cells that recognize this portion of the insulin molecule may arise in the thymus by deletion of T cells that recognize similar peptides.
Miller
G G
GG
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Hoy
J F
JF
Thomas
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007328:Insulin / Q000031:analogs & derivatives / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013950:Thymus Gland / Q000032:analysis*
D000939:Epitopes; D007127:Immunoglobulin Constant Regions; D007328:Insulin; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell