Receptor for α1-Microglobulin on T Lymphocytes: Inhibition of Antigen-Induced Interleukin-2 Production |
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Authors: | Wester Michaëlsson Holmdahl Olofsson & Åkerström |
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Institution: | Section for Molecular Signalling; Medical Inflammation Research, Department of Cell and Molecular Biology; Division of Haematology, Department of Medicine, Lund University, Lund, Sweden |
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Abstract: | The human plasma protein α1-microglobulin (α1m) was found to inhibit the antigen-induced interleukin-2 (IL-2) production of two different mouse T-helper cell hybridomas. α1m isolated from human plasma and recombinant α1m isolated from baculovirus-infected insect cell cultures had similar inhibitory effects. Flow cytometric analysis showed a binding of plasma and recombinant α1m to the T-cell hybridomas as well as to a human T-cell line. Radiolabelled plasma and recombinant α1m bound to the T-cell hybridomas in a saturable manner and the binding could be eliminated by trypsination of the cells. The affinity constants for the cell binding were calculated to be 0.4–1 × 105 M ?1 using Scatchard plotting, and the number of binding sites per cell was estimated to be 5 × 105–1 × 106. The cell-surface proteins of one of the T-cell hybridomas were radiolabelled, the cells lysed and α1m-binding proteins isolated by affinity chromatography. SDS–PAGE and autoradiography analysis of the eluate revealed major bands with M r-values around 70, 35 and 15 kDa. The results thus suggest that α1m binds to a specific receptor on T cells and that the binding leads to inhibition of antigen-stimulated IL-2 production by T-helper cells. |
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