Structure-function relationships for the IL 2-receptor system. I. Localization of a receptor binding site on IL 2

Interleukin 2 (IL 2) modulates the growth and differentiation of a variety of lymphocyte subclasses through its interaction with a specific cell surface receptor. Although both IL 2 and its receptor have been characterized extensively, the location of interaction sites on the two molecules is unknown. Synthetic peptides based on the IL 2 sequence were used to determine the epitopes seen by a number of antibodies reactive with IL 2, some of which inhibited the receptor binding of the factor and the proliferative response of target cells. The results indicated that inhibitory antibodies bound at either of two spatially distinct sites defined by amino acids 8-27 and 33-54. By inference, these segments may also encode distinct contact sites for receptor association. Alternatively, a single contact site may be located between the antibody epitopes in the three-dimensional configuration of the molecule. Although the data did not directly address the role of the C-terminal portion of IL 2, this preliminary localization of receptor contact sites within the N-terminal half of the molecule should prove useful in correlating structure and function during crystallographic analysis of the factor.