The insulin-specific T cells of nonobese diabetic mice recognize a weak MHC-binding segment in more than one form.
Several naturally occurring anti-insulin CD4 T cells were isolated from islet infiltrates of NOD mice. In accordance with the results of others, these T cells recognized the segment of the beta-chain from residues 9-23. Peptides encompassing the B:(9-23) sequence bound weakly to I-Ag7 in two main contiguous registers in which two residues at the carboxyl end, P20Gly and P21Glu, influenced binding and T cell reactivity. Naturally occurring insulin-reactive T cells exhibited differing reactivities with the carboxyl-terminal amino acids, although various single residue changes in either the flanks or the core segments affected T cell responses. The insulin peptides represent another example of a weak MHC-binding ligand that is highly immunogenic, giving rise to distinct populations of autoimmune T cells.
Levisetti
Matteo G
MG
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Suri
Anish
A
Petzold
Shirley J
SJ
Unanue
Emil R
ER
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D018920:Coculture Techniques; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000276:immunology* / Q000378:metabolism*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D011236:Prediabetic State / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000276:immunology; D020033:Protein Isoforms / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen; D007328:Insulin; D008024:Ligands; D010446:Peptide Fragments; D020033:Protein Isoforms; C097877:insulin B (9-23)