A regulatory role for the soluble IL-2 receptor via competition with the p75 cell-surface form of the receptor for IL-2.
Murine T and B lymphocytes can be induced to release soluble interleukin 2 receptors (sIL2R). This receptor is believed to be a truncated form of the p55 chain of the cell membrane-associated receptor. It has been speculated that this receptor may play an immunoregulatory role via competition for IL-2 with the high-affinity (p55/75 heterodimer) IL-2 receptor. Of crucial importance to this hypothesis are both the concentration of the receptor and its affinity of binding for interleukin 2. We report the measurement of the affinity of sIL2R derived from stimulated normal murine splenocytes for IL-2. We also report the quantification of an enzyme linked immunosorbent assay (ELISA) for sIL2R via measurement of the sIL2R concentration in normal murine splenocyte conditioned medium using a radioimmunometric assay and Scatchard analysis. This method of sIL2R quantification is preferable to sIL2R purification and subsequent concentration estimation as used by previous investigators as any purification process risks destruction of some epitopes. Using the above conditioned medium as a standard we have tested supernatants from several cell lines and sera from several different mouse strains for sIL2R. As would be expected this method of quantification yielded a markedly different value for serum sIL2R levels in normal mice than that obtained by previous investigators. Our results indicate that it is very unlikely that sIL2R competes with the high-affinity form of the IL-2 receptor for IL-2. However, it is possible that it competes for IL-2 with the medium-affinity p75 form of the IL-2 receptor and as such is important in restricting unwanted non-specific (bystander) activation of p75 expressing cells. Evidence from both our previous work as well as from the literature is presented to support this hypothesis.
Loughnan
M S
MS
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Nossal
G J
GJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001667:Binding, Competitive; D004797:Enzyme-Linked Immunosorbent Assay; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D011863:Radioimmunoassay; D011869:Radioligand Assay; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2