title: TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs.
abstract: Ig-PLP1 and Ig-PLP-LR are chimeric Igs expressing proteolipid protein (PLP)-derived T cell agonist (PLP1) and antagonist (PLP-LR) peptides, respectively. Both chimeras, like free PLP1 and PLP-LR peptides, induce in vivo-specific T cell responses. However, the responses induced by Ig-PLP1 and Ig-PLP-LR were cross-reactive with both PLP1 and PLP-LR peptides, while those induced by free peptides were not. Surprisingly, despite the cross-reactivity of the responses, when Ig-PLP1 and Ig-PLP-LR were administered together into mice, a dose-dependent down-regulation of both T cell responses and a reduction of IL-2 production to background levels was observed. In contrast, when T cells induced by either Ig chimera were stimulated in vitro with mixtures of free PLP1 and PLP-LR peptides, there was no down-regulation of proliferation or decrease in IL-2 production. These data indicate that Ig-PLP1 and Ig-PLP-LR exert adverse reactions on one another at the level of naive T cells, resulting in an opposite antagonism. However, naive T cells experiencing either chimera develop into cross-reactive cells, acquire resistance to TCR triggering by closely related but different peptides, and support responsiveness.
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville 37996, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Legge
authors.forename: B
authors.initials: B
authors.lastname: Min
authors.forename: A E
authors.initials: AE
authors.lastname: Cestra
authors.forename: C D
authors.initials: CD
authors.lastname: Pack
authors.forename: H
authors.initials: H
authors.lastname: Zaghouani
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D007136:Immunoglobulins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins