IL-2, a lectin with specificity for high mannose glycopeptides

Area of Science:

• Biochemistry
• Immunology
• Glycobiology

Background:

• Interleukin-2 (IL-2) is a cytokine crucial for immune responses.
• Uromodulin is a glycoprotein found in human urine with incompletely understood functions.
• The potential for IL-2 to interact with non-protein targets is largely unexplored.

Purpose of the Study:

• To investigate the binding properties of recombinant IL-2 (rIL-2) beyond its known receptor interactions.
• To determine if rIL-2 exhibits carbohydrate-binding activity (lectin-like properties).
• To explore the physiological relevance of any identified carbohydrate-binding activity.

Main Methods:

• Solid phase binding assays were employed to assess rIL-2 interactions.
• Inhibition studies using various saccharides and glycopeptides were performed.
• Sequence homology analysis was conducted between IL-2 and known carbohydrate-binding proteins.
• Binding studies were performed under varying pH conditions and in the presence of divalent cations.

Main Results:

• rIL-2 demonstrated high-affinity binding to human uromodulin.
• This binding was specifically inhibited by certain mannose-containing saccharides and glycopeptides.
• rIL-2 also bound to other mannose-rich glycoproteins like OVA and yeast mannan.
• Sequence analysis revealed homology between IL-2 and the carbohydrate-binding domain of mannose-binding protein.
• rIL-2 binding to uromodulin was enhanced at acidic pH (4-5) with divalent cations.
• Uromodulin and specific glycopeptides did not block rIL-2 binding to the IL-2 receptor.

Conclusions:

• rIL-2 possesses lectin-like carbohydrate-binding activity, distinct from its receptor-binding function.
• The carbohydrate-binding site of rIL-2 may preferentially function in acidic microenvironments.
• These findings suggest novel roles for IL-2 beyond T-cell activation, potentially involving innate immunity or tissue interactions.