Inhibition of an in vitro CD4+ T cell alloresponse using altered peptide ligands.
In this study, we explore the potential of altered peptide ligands (APLs) to modulate the alloresponse of CD4+ T cells using elements of the murine hemoglobin (Hb) Ag model. We first demonstrated that the T cell 2.102, specific for the Hb(64-76)/I-Ek complex, was alloreactive against splenocytes of the H-2p haplotype. Using Ab-blocking and transfection experiments, we further showed that this alloreactivity was restricted to the class II molecule I-Ep. We tested a panel of APLs previously shown to antagonize the Hb response of 2.102 and found that these peptides could also effectively inhibit the alloresponse to I-Ep. Importantly, these peptides were able to antagonize the alloresponse of naive T cells derived from mice transgenic for the 2.102 TCR, as well as Th1 and Th2 cell lines. The antagonism required the presence of both I-Ep and I-Ek on the same APC. Our study demonstrates the effectiveness of APLs to antagonize the primary alloresponse of specific T cells and provides a basis for the development of immunotherapeutics for use in transplantation and immune-mediated diseases.
Daniel
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Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Grakoui
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A
Allen
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PM
D019943:Amino Acid Substitution; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006454:Hemoglobins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology*; D006825:Hybridomas; D007166:Immunosuppressive Agents / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007399:Interphase / Q000276:immunology; D008024:Ligands; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
D000939:Epitopes; D006454:Hemoglobins; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007166:Immunosuppressive Agents; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C079201:hemoglobin (64-76)