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.