Structural Studies of T200 Glycoprotein and the Il-2 Receptor

Abstract

Immunological analysis of the cell surface of hematopoietic cells has led to the identification of many different cell membrane molecules, some of which have well-defined functions as receptors. In general, however, the role of most lymphocyte cell surface molecules remains ill-defined even in cases in which antibody inhibition studies have given some insight into the biological processes in which they participate. Here we describe molecular and biochemical studies of T200 glycoprotein (leukocyte-common antigen) and the IL-2 receptor which illustrate the kinds of approaches that can be currently used to characterize individual molecules. T200 glycoprotein is a large M_r glycoprotein found exclusively on leukocytes. However, the exact M_r varies in a cell-type-specific fashion and this property is conserved between different species. Comparison of the rat, mouse and human cDNA sequences show that the large cytoplasmic portion of the molecule is well-conserved, approximately 90%, whereas the exterior portion is only about 50% homologous. Cell-type-specific differences in the primary sequence of the molecule have been identified in the N-terminal portion of the molecules. In contrast to T200, the function of the IL-2 receptor is well-known. The interaction of IL-2 with its receptor provides a growth signal that determines the magnitude and duration of T-cell responses. Limited proteolysis studies provide the first direct biochemical evidence that the external region of the IL-2 receptor consists of two independent domains. ¹²⁵I-labeled IL-2 has been chemically crosslinked to the receptor and proteolytic cleavage of the crosslinked product indicates that IL-2 is selectively bound to the N-terminal domain of the receptor.