Receptor for alpha1-microglobulin on T lymphocytes: inhibition of antigen-induced interleukin-2 production.
The human plasma protein alpha1-microglobulin (alpha1m) was found to inhibit the antigen-induced interleukin-2 (IL-2) production of two different mouse T-helper cell hybridomas. Alpha1m isolated from human plasma and recombinant alpha1m isolated from baculovirus-infected insect cell cultures had similar inhibitory effects. Flow cytometric analysis showed a binding of plasma and recombinant alpha1m to the T-cell hybridomas as well as to a human T-cell line. Radiolabelled plasma and recombinant alpha1m 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 x 10(5) M(-1) using Scatchard plotting, and the number of binding sites per cell was estimated to be 5 x 10(5)-1 x 10(6). The cell-surface proteins of one of the T-cell hybridomas were radiolabelled, the cells lysed and alpha1m-binding proteins isolated by affinity chromatography. SDS-PAGE and autoradiography analysis of the eluate revealed major bands with Mr-values around 70, 35 and 15 kDa. The results thus suggest that alpha1m 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.
Section for Molecular Signalling, Lund University, Sweden.
L
L
Wester
E
E
Michaëlsson
R
R
Holmdahl
T
T
Olofsson
B
B
Akerström
D000510:Alpha-Globulins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology; D003094:Collagen / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D011971:Receptors, Immunologic / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000510:Alpha-Globulins; D000941:Antigens; D007376:Interleukin-2; D011971:Receptors, Immunologic; C057015:alpha(1)-microglobulin receptor; C016001:alpha-1-microglobulin; D003094:Collagen