Interleukin 1 alpha and interleukin 1 beta bind to the same receptor on T cells

• Published in: The Journal of immunology (1950) Vol. 136; no. 12; pp. 4509 - 4514
• Main Authors: Kilian, PL, Kaffka, KL, Stern, AS, Woehle, D, Benjamin, WR, Dechiara, TM, Gubler, U, Farrar, JJ, Mizel, SB, Lomedico, PT
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.06.1986; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Binding, Competitive; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Interleukin-1 - metabolism; Interleukin-1 - physiology; Kinetics; Lymphokines, interleukins ( function, expression); Mice; Receptors, Antigen, T-Cell - analysis; Receptors, Antigen, T-Cell - drug effects; Receptors, Antigen, T-Cell - metabolism; Receptors, Immunologic - analysis; Receptors, Immunologic - drug effects; Receptors, Immunologic - metabolism; Receptors, Interleukin-1; Recombinant Proteins - metabolism; Regulatory factors and their cellular receptors; T-Lymphocytes - metabolism; Human; Vertebrata; Membrane receptor; Mammalia; Mouse; Rodentia; Interleukin 1; T-Lymphocyte; Molecular interaction
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.136.12.4509

Pure, E. coli-derived recombinant murine interleukin 1 alpha (IL 1 alpha) was labeled with 125I and used for receptor binding studies. The 125I-IL 1 binds to murine EL-4 thymoma cells in a specific and saturable manner. Scatchard plot analysis for binding studies carried out at 4 degrees C reveals a single type of high affinity binding site with an apparent dissociation constant of approximately 2.6 X 10(-10) M and the presence of approximately 1200 binding sites per cell. The rate of association of the 125I-IL 1 with EL-4 cells is slow, requiring more than 3 h to reach apparent steady state at 4 degrees C. Cell-bound 125I-IL 1 cannot be dissociated from EL-4 cells upon removal of unbound 125I-IL 1 and incubation of the cells at 4 degrees C in the presence or absence of unlabeled IL 1. Unlabeled recombinant murine IL 1 competes for 125I-IL 1 binding in a dose-dependent manner, whereas interferon-alpha A, interleukin 2 (IL 2), epidermal growth factor, and nerve growth factor have no effect. The 125I-IL 1 binding site is sensitive to trypsin, suggesting that it is localized on the cell surface. We have also examined the ability of purified recombinant human IL 1 alpha and IL 1 beta to compete for binding of the radiolabeled murine IL 1 to its receptor and to stimulate IL 2 production by EL-4 cells. Previous reports have shown that human IL 1 alpha is approximately 60% homologous in amino acid sequence with murine IL 1, but that human IL 1 beta is only about 25% homologous with either murine IL 1 or human IL 1 alpha. Despite these marked differences, however, we report here that both human IL 1 proteins are able to recognize the same binding site as mouse IL 1. In addition, murine as well as both human IL 1 proteins stimulate IL 2 production by EL-4 cells.