TY - JOUR
T1 - TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs
AU - Legge, Kevin L.
AU - Min, Booki
AU - Cestra, Aimee E.
AU - Pack, Christopher D.
AU - Zaghouani, Habib
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/7/1
Y1 - 1998/7/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.161.1.106
DO - 10.4049/jimmunol.161.1.106
M3 - Article
C2 - 9647213
AN - SCOPUS:0031803343
SN - 0022-1767
VL - 161
SP - 106
EP - 111
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -