High-affinity interleukin 2 receptor alpha and beta chains are internalized and remain associated inside the cells after interleukin 2 endocytosis.

Abstract

High-affinity interleukin 2 (IL2) receptors on humanT lymphocytes are multimeric complexes containing two IL2-binding polypeptides, a and @ chains of 50-55 and 70-75 kDa, respectively, associated by noncovalent bonds.IL2 binds to high-affinity IL2 receptors on the surface of T lymphocytes, mediates cell growth, and is internalized.In this paper, we used a biochemical method to directly identify the receptors components internalized together with the ligand.12'I-IL2receptor complexes were solubilized with the detergent 3-[(3-cholamidopropyI)dimethylammonio]-l-propanesulfonate, and IL2-binding polypeptides were identified by cross-linking with disuccinimidyl suberate.Under such conditions, the noncovalent association between a and @ is maintained.After IL2 internalization, two complexes of about 70 and 90 kDa, IL2 crosslinked to a and B, respectively, were found inside the cells.Both components were immunoprecipitated with either anti-a or anti-@ monoclonal antibodies.This shows that the a and @ chains are found in an intracellular compartment after IL2 endocytosis, and remain associated as a ternary complex with IL2.Interleukin 2 (IL2),' a growth factor for T lymphocytes, transduces the growth signal through a specific receptor complex that binds IL2 with high affinity ( K d , 10-100 PM) (1-3).The high-affinity receptor complex consists of at least two distinct receptor components, the a chain of 50-55 kDa (4-8), and the p chain of 70-75 kDa (9-13).a and p polypeptides, when expressed on the cell surface without / 3 and a , respectively, bind IL2 with a lower affinity.They form low and intermediate affinity receptors, with dissociation constants of 10 and 1 nM, respectively.The very high affinity of functional receptors for the ligand is due to the combination of two properties of individual chains, the high association rate of IL2 to a chains, and the slow dissociation of IL2 to ( 3 chains (14, 15). a and ( I subunits are bound by noncovalent association to form high-affinity receptors (16), the structure of which has not been further determined.In addition to a and p, the ~5 6 ' ' ~ tyrosine kinase is associated to the p chain and