Document Type

Article

Publication Date

2-1985

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Department

Geisel School of Medicine

Abstract

The cell surface density of high-affinity membrane receptors for the T-lymphocytotrophic hormone interleukin 2 (IL-2) determines the rate of T-cell-cycle progression. Since 10-fold greater numbers of IL-2 receptor molecules were found by using a radiolabeled monoclonal antibody reactive with IL-2 receptors (anti-Tac) compared with binding of IL-2, the functional relationship of the binding sites recognized by both of these ligands was assessed. In the presence of cycloheximide, IL-2 binding sites declined with a half-time (t1/2) of 2.6 hr, whereas the decay of anti-Tac binding sites was much slower (t 1/2 = 6.4 hr). Moreover, after limited membrane proteolysis, the half-time for the reappearance of IL-2 binding sites was remarkably similar to its decay (t 1/2 = 2.2 hr), while Tac antigen reappearance was markedly retarded, returning to only 20% of original levels within 5 hr after proteolysis. Addition of homogeneous immunoaffinity-purified IL-2 to cell populations that expressed equivalent IL-2 and anti-Tac binding sites resulted in a time- and temperature-dependent 8- to 10-fold enhancement of Tac epitope expression and, simultaneously, a 20-30% diminishment of detectable high-affinity IL-2 binding sites. As the magnitude of the IL-2-dependent proliferative response correlated with the density of high-affinity IL-2 binding sites, rather than Tac antigen levels, quantitation of Tac epitope density does not provide a reliable indication of IL-2-responsiveness among activated T-cell populations. Instead, IL-2-receptor interactions actually promote the loss of IL-2 responsiveness by diminishing the density of high-affinity binding sites at the time that Tac antigen levels are increased.

Original Citation

Smith KA, Cantrell DA. Interleukin 2 regulates its own receptors. Proc Natl Acad Sci U S A. 1985;82(3):864-868. doi:10.1073/pnas.82.3.864

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