Interleukin 2 and its cell-surface receptor

Abstract

Interleukin 2 provides a signal for the proliferation and differentiation of several classes of immune cells, including activated T cells, natural killer cells and certain activated B cells. The responses to this lymphokine result from its interaction with a high-affinity cell surface receptor. Several structural features of the IL-2 molecule are essential for its functional integrity. For example, an intramolecular disulfide bridge connecting cysteine residues in positions 58 and 105 maintains an active conformation of the molecule. In addition, antibodies directed against epitopes defined by amino acids 8-27 and 33-54 are capable of directly blocking the physiological response. Amino acids in or near these regions may form part of the receptor binding site of IL-2. The receptor for IL-2 exists in both high and low-affinity states. Physiological responses correlate with binding to the high-affinity form of the receptor as determined by anti-IL-2 antibody competition curves. Expression of the cDNA corresponding to the receptor protein in mouse L cells, however, indicates that this protein alone is incapable of high-affinity interaction with IL-2. Thus, the high-affinity conformation of the receptor may entail the interaction of the ligand-binding component with an additional receptor subunit(s). The availability of pure ligand and receptor as well as antibody reagents to both these components make the IL-2 receptor system an ideal model for dissecting an immune response at the molecular level.