Mutation of Asp20 of human interleukin‐2 reveals a dual role of the p55 α chain of the interleukin‐2 receptor

Claudia L. Flemming, Stephen J. Russell, Mary K.L. Collins

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Mutation of Asp20 in human interleukin‐2 (IL‐2) to Lys is known to result in an IL‐2 molecule with unchanged binding to the p55 subunit of the IL‐2 receptor, but with greatly decreased affinity for the p75 subunit (Collins, L., Tsien, W.‐H., Seals, C. et al. Proc. Natl. Acad. Sci USA 1988. 85: 7709). Here we demonstrate that Lys20 IL‐2 competed with a reduced (10‐fold) affinity for high‐affinity IL‐2 receptors on two murine cell lines HT2 and CTLL. In parallel with this difference in receptor interaction, Lys20 IL‐2 stimulated half‐maximal HT2 cell proliferation at a 10‐fold higher concentration than wild‐type IL‐2. However, half‐maximal stimulation of CTLL cells required a 100‐fold higher concentration of Lys20 IL‐2. A similar 100‐fold reduction in bioactivity of Lys20 IL‐2 was observed for primary, activated, human or murine lymphocytes. Anti‐p55 antibodies increased the concentration of Lys20 IL‐2 required to stimulate HT2 cells to that required for CTLL cells. These data suggest that CTLL cells, while able to bind Lys20 IL‐2 with high affinity, are lacking a p55‐dependent function necessary for optimal stimulation. Therefore, p55 has a dual role, being important both for high‐affinity IL‐2 binding and for optimal cell triggering.

Original languageEnglish (US)
Pages (from-to)917-921
Number of pages5
JournalEuropean Journal of Immunology
Issue number4
StatePublished - Apr 1993


  • Interleukin‐2
  • Mutational analysis
  • Receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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