Differential signaling and hierarchical response thresholds induced by an immunodominant peptide of myelin basic protein and an altered peptide ligand in human T cells

• Published in: Human immunology 1998-11, Vol.59 (11), p.679-689
• Main Authors: Crowe, Paul D, Boehme, Stefen A, Wong, Tim, Gaur, Amitabh, Sidney, John, Sette, Alessandro, Conlon, Paul J
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Amino Acid Substitution; B-Lymphocytes; Binding Sites; Cell Division; Cell Line; Coculture Techniques; Cytokines - biosynthesis; GRB2 Adaptor Protein; HLA-DR Antigens - metabolism; HLA-DRB1 Chains; Humans; Immunodominant Epitopes; Membrane Proteins - immunology; Membrane Proteins - metabolism; Molecular Sequence Data; Myelin Basic Protein - chemistry; Myelin Basic Protein - immunology; Peptide Fragments - chemistry; Peptide Fragments - immunology; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Proteins - metabolism; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; src-Family Kinases - metabolism; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology; ZAP-70 Protein-Tyrosine Kinase
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/S0198-8859(98)00077-9

Changes in peptide antigen concentration or structure can have a profound effect on T cell responsiveness by inducing selected T cell effector functions. In this study, we have compared the biological responses of an MBP83-99-specific human T h0 T cell clone (TCC) stimulated with increasing concentrations of native peptide or an altered peptide ligand (APL). Our results show that the hierarchy of response thresholds for proliferation and cytokine secretion is similar for native peptide and APL. However, because a much higher concentration of the APL is required to evoke the same degree of response, the cytokine profile is shifted towards a T h2-like response relative to the same concentration of native peptide. In addition, we observed qualitative differences in TCR signal transduction triggered by native peptide and a weak agonist APL even at concentrations that elicit similar biological responses. Thus, the relationship between TCR signaling and biological responses may be more complex than previously recognized.