ENDOCYTOSIS OF INTERLEUKIN-2 RECEPTORS IN HUMAN T-LYMPHOCYTES - DISTINCT INTRACELLULAR-LOCALIZATION AND FATE OF THE RECEPTOR ALPHA-CHAIN, BETA-CHAIN, AND GAMMA-CHAIN

Members of the cytokine receptor family are composed of several noncov alently linked chains with sequence and structure homologies in their extracellular domain. Receptor subfamily members share at least one co mponent: thus the receptors for interleukin (IL) 2 and IL15 have commo n beta and gamma chains, while those for IL2, 4, 7, and 9 have a commo n gamma chain. The intracellular pathway followed by IL2 receptors aft er ligand binding and endocytosis was analyzed by immunofluorescence a nd confocal microscopy in a human T lymphocytic cell line. Surprisingl y, the alpha, beta, and gamma chains had different intracellular local izations after being endocytosed together. The alpha chain was always in transferrin-positive compartments (early/recycling endosomes), both at early and late internalization times, but was never detected in ra b7-positive compartments (late endosomes). On the other hand, at late internalization times, the beta and gamma chains were excluded from tr ansferrin-positive organelles and did not colocalize with alpha. Furth ermore, beta could be found in rab7-positive vesicles. These differenc es suggest that the alpha chain recycles to the plasma membrane, while the beta and gamma chains are sorted towards the degradation pathway. The half-lives of these three chains on the cell surface also reflect their different intracellular fates after endocytosis. The beta and g amma chains are very short-lived polypeptides since their half-life on the surface is only approximate to 1 h, whereas ar is a much more sta ble surface protein. This shows for the first time that components of a multimeric receptor can be sorted separately along the endocytic pat hway.