The lack of consensus for I-A(g7)-peptide binding motifs: is there a requirement for anchor amino acid side chains?
We discuss here the problems in identifying sequence motifs of peptides that bind to I-A(g7), the class II histocompatibility molecule of NOD diabetic mice. We present studies that indicate a minor contribution of amino acid side chains for binding. A peptide from the Ealpha chain binds to I-A(g7) molecules and is recognized by CD4 T cells. By producing single-residue mutations we identified four residues that were considered to contact the T cell receptor. No residue was found to be essential for binding to I-A(g7): a peptide that contained the T cell contact residues, on a backbone of alanines, bound to I-A(g7) and stimulated the T cells. We conclude that peptides can bind to I-A(g7) without the requirement for residues with prominent side chains to anchor them.
Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
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Carrasco-Marin
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Kanagawa
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Unanue
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D009154:Mutation; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C117647:antigenic peptide Ealpha52-68; C019529:polyalanine; D010047:Ovalbumin