Abstract
Interleukin 2 (IL-2) interacts with a receptor (IL-2R) composed of three subunits (IL-2Rα, IL-2Rβ and IL-2Rγ). IL-2Rβ plays a critical role in signal transduction. An anti-human IL-2 mAb (H2-8) produced after immunization with peptide 1-30 of IL-2 was found to recognize the region occupied by Asp20, at the exposed interface between α-helices A and C. Muteins at position 17 and 20 are not recognized by mAb H2-8. mAb H2-8 specifically inhibits the IL-2 proliferation of TS1β cells which are dependent on the expression of human Il-2Rβ chain for IL-2 proliferation. Substitution at internal position Leu17 demonstrated that this position is essential for IL-2 binding and IL-2 bioactivity. New IL-2 mutants at position Asp20 have been analysed. Substitutions Asp→Asn, Asp→Lys, Asp→Leu, show a correlation between diminished affinity for IL-2 receptor and reduced bioactivity measured on TS1β cells. Mutein Asp→Arg lose affinity for IL-2R and bioactivity simultaneously. Furthermore, during the course of the study we have found that mutein Asp20→Leu is an IL-2 antagonist. The biological effects of mAb H2-8 and the properties of new mutants at positions 17 and 20 demonstrate that this region of α helix-A is involved in IL-2–IL-2Rβ interactions.
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