The activation of pigeon cytochrome c-specific T cell hybridomas by antigenic peptides is influenced by non-native sequences at the amino terminus of the determinant.
We recently demonstrated that the sequence 95-104 contains all the residues necessary for direct recognition of the I-Ek restricted pigeon cytochrome c determinant but that residues located in sequences to the amino-terminal side of residue 95 improve the ability of peptides containing the sequence 95-104 to stimulate Ag-specific T cell clones. In this study we use synthetic peptides with amino-terminal leader sequences containing residues that differ with respect to their conformational stabilizing effects, charge, and hydrophilicity to examine the mechanism by which they modulate T cell recognition. Our findings indicate that the role of these residues in T cell stimulation is not related to their ability to stabilize alpha-helical secondary structure, nor do they appear to be processed differently. The leader sequences do not differentially influence the ability of the peptides to be presented by APC displaying Ia molecules of related haplotype, i.e., E alpha kE beta k, E alpha kE beta b, and E alpha kE beta s, to T cells which recognize the pigeon cytochrome c determinant on such presenting cells. Because antigenic potency correlates with the inclusion of hydrophobic residues and positively charged residues in the leader sequences, we discuss our findings with reference to the possibility that they non-specifically enhance the interaction of the antigenic peptides with the APC membrane.
Bhayani
H
H
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Carbone
F R
FR
Paterson
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000145:classification / Q000276:immunology; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology*; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II; D006825:Hybridomas / Q000032:analysis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011487:Protein Conformation; D021382:Protein Sorting Signals / Q000276:immunology; D013601:T-Lymphocytes / Q000032:analysis / Q000276:immunology*
D003574:Cytochrome c Group; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010455:Peptides; D021382:Protein Sorting Signals