Increasing the biological activity of IL-2 and IL-15 through complexing with anti-IL-2 mAbs and IL-15R伪-Fc chimera

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• 作者：Petra VotavovaAuthor Vitae ; Jakub TomalaAuthor Vitae ; Marek Kovar ; ^{makovar@biomed.cas.cz" class="auth_mail}Author Vitae
• 关键词：IL-2 ; IL-15 ; Anti-IL-2 mAb ; IL-15R伪-Fc chimera ; Immunocomplexes ; Biological activity
• 刊名：Immunology Letters
• 出版年：May-June, 2014
• 年：2014
• 卷：159
• 期：1-2
• 页码：1-10
• 全文大小：1335 K

文摘

IL-2 and IL-15 are structurally relative cytokines that share two receptor subunits, CD132 (纬_c chain) and CD122 (尾 chain). However, the expression pattern and physiological role of IL-2 and IL-15 private receptor 伪 chains CD25 and IL-15R伪, respectively, are strikingly different. CD25, together with CD122 and CD132, forms a trimeric high affinity IL-2 receptor that is expressed and functions on cells acquiring an IL-2 signal. Conversely, IL-15R伪 is expressed and binds IL-15 with high affinity per se already in the endoplasmic reticulum of the IL-15 producing cells and it presents IL-15 to cells expressing CD122/CD132 dimeric receptor in trans. Thus, while IL-2 is secreted almost exclusively by activated T cells and acts as a free molecule, IL-15 is expressed mostly by myeloid cells and works as a cell surface-associated cytokine. Interestingly, the in vivo biological activity of IL-2 can be dramatically increased through complexing with certain anti-IL-2 mAbs; such IL-2/anti-IL-2 mAbs immunocomplexes selectively stimulate the proliferation of a distinct population of immune cells, depending on the clone of the anti-IL-2 mAb used. IL-2/S4B6 mAb immunocomplexes are highly stimulatory for CD122^high populations (memory CD8⁺ T and NK cells) and intermediately also for CD25^high populations (Treg and activated T cells), while IL-2/JES6-1 mAb immunocomplexes enormously expand only CD25^high cells. Although IL-2 immunocomplexes are much more potent than IL-2 in vivo, they show comparable to slightly lower activity in vitro. The in vivo biological activity of IL-15 can be dramatically increased through complexing with recombinant IL-15R伪-Fc chimera; however, IL-15/IL-15R伪-Fc complexes are significantly more potent than IL-15 both in vivo and in vitro. In this review we summarize and discuss the features and biological relevance of IL-2/anti-IL-2 mAbs and IL-15/IL-15R伪-Fc complexes, and try to foreshadow their potential in immunological research and immunotherapy.