Species specificity of interleukin 2 binding to individual receptor components.

Abstract

The affinity of recombinant human and murine interleukin 2 (IL 2), which differ significantly in structure in the amino terminal alpha helix, for the human or murine interleukin 2 receptors was compared. Murine IL 2 showed a 10-fold higher affinity than human IL 2 for the murine high-affinity receptor expressed on T lymphocytes, whereas human IL 2 bound 100-fold more strongly than murine IL 2 to the human high-affinity receptor. As the high-affinity IL 2 receptor on T lymphocytes has been demonstrated to be composed of two IL 2 binding components, p55 and p75, the role of the individual chains in the determination of species specificity was then investigated. Recombinant retroviral vectors were used to generate populations of 3T3 fibroblasts expressing either human or murine p55 in isolation, and their binding characteristics were determined. While the murine p55 showed an identical species preference to the murine p55/p75 high-affinity complex, the human p55 had an equal affinity for human and murine IL 2. This suggested that the human p75 chain was responsible for the preference for human IL 2 shown by the human high-affinity receptor, which was confirmed by performing a binding experiment using gibbon MLA 144 cells, expressing only p75. These data suggest that the amino terminal region of the IL 2 molecule interacts with the p75 chain of the IL 2 receptor.