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IL2-CD25 aptermer
Timeline
Review recent work concerning the structure, signaling, and function of the IL-2R, emphasizing the contribution of IL-2 for T cell-dependent activity in vivo.[2]
Performed gene expression and immunochemical analyses. RT-PCR revealed no IL-2 gene expression in cultured ALCL cells and ruled out the possibility of an IL-2 autocrine loop.[3]
Determined the effects of sIL-2Rα on IL-2 signaling and found that the sIL-2Rα-IL-2 complex promoted T-cell differentiation toward to inhibitory T(reg) cells rather than T(H)1 or T(H)17 cells. [4]
Description
In 2019, RNA aptamer-based assay platform designated as the "LIgand-REceptor Complex-binding APtamer," or "LIRECAP," assay that allows for quantification of the fraction of receptors occupied by a ligand was developed and used to measure the fraction of soluble CD25 occupied by IL2 in the serum of subjects with B-cell lymphoma[10].SELEX
In 2019, RNA aptamer-based assay platform designated as the "LIgand-REceptor Complex-binding APtamer," or "LIRECAP," assay that allows for quantification of the fraction of receptors occupied by a ligand was developed and used to measure the fraction of soluble CD25 occupied by IL2 in the serum of subjects with B-cell lymphoma[10].
Detailed information are accessible on SELEX page.
Structure
The 2D structure of the figure is based on the article by ribodraw tool to draw[10].5'-GGGAGGACGAUGCGGUGAGUCGUUCCCUUCGUCCCCAGACGACUCGCCCGA-3'
Ligand information
SELEX ligand
The Interleukin-2 receptor alpha chain (also called TAC antigen, P55, and mainly CD25) is a protein involved in the assembly of the high-affinity Interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with Interleukin-2, a pleiotropic cytokine which plays an important role in immune homeostasis.-----from WiKi
| Name | Uniprot ID | Pfam | MW | Amino acids sequences | PDB | Gene ID |
|---|---|---|---|---|---|---|
| Interleukin-2 receptor subunit alpha | P01589 | IPR015486 | 30.819kDa | MDSYLLMWGLLTFIMVPGCQAELCDDDPPEIPHATFKAMAYKEGTMLNCECKRGFRRIKSGSLYMLCTGNSSHSSWDNQCQCTSSATRNTTKQVTPQPEEQKERKTTEMQSPMQPVDQASLPGHCREPPPWENEATERIYHFVVGQMVYYQCVQGYRALHRGPAESVCKMTHGKTRWTQPQLICTGEMETSQFPGEEKPQASPEGRPESETSCLVTTTDFQIQTEMAATMETSIFTTEYQVAVAGCVFLLISVLLLSGLTWQRRQRKSRRTI | 1Z92 | NM_001310816.1 |
Binding kinetics of aptamers confirm differential binding to CD25 versus IL2-CD25 complex.The binding kinetics of the aptamers toward CD25 and the IL2-CD25 complex, including association and dissociation kinetics, were determined using biolayer interferometry. The Kd, Kon, and Kdis rates for aptamer binding are summarized in Table 1 and the sensorgram in Supplementary Fig. S2. Tr-1 and Tr-7 that bound preferentially to the complex displayed a stronger affinity (lower Kd) for the IL2-CD25 complex than for the unoccupied CD25, whereas Tr-6 and Tr-8 that bound preferentially to unoccupied CD25 showed weaker affinity (higher Kd) for the IL2-CD25 complex than for unoccupied CD25. The Tr-11 aptamer that bound to the receptor and the complex equally displayed similar affinities for both (Table 1). Thus, differential affinity of aptamers for IL2-CD25 complex versus unoccupied CD25 was consistent with their differential binding preferences[10].
| Name | Sequence | Ligand | Affinity |
|---|---|---|---|
| Tr-1 | 5'-GGGAGGACGAUGCGGUCCUGUCGUCUGUUCGUCCCCAGACGACUCGCCCGA-3' | CD25 protein | 122.0 nM |
| Tr-6 | 5'-GGGAGGACGAUGCGGCGUUUCCUCUGGUUCGUCCCCAGACGACUCGCCCGA-3' | CD25 protein | 96.9 nM |
| Tr-7 | 5'-GGGAGGACGAUGCGGUGAGUCGUUCCCUUCGUCCCCAGACGACUCGCCCGA-3' | CD25 protein | 68.2 nM |
| Tr-8 | 5'-GGGAGGACGAUGCGGGCCGUUGUUGUGUGCCGCCCCAGACGACUCGCCCGA-3' | CD25 protein | 35.7 nM |
| Tr-11 | 5'-GGGAGGACGAUGCGGAUUCUGGUUACUGGCCGCCCCAGACGACUCGCCCGA-3' | CD25 protein | 46.1 nM |
Similar compound
We used the Dail server website to compare the structural similarities of ligand proteins, and chose the top 10 in terms of similarity for presentation. The Dali server is a network service for comparing protein structures in 3D. Dali compares them against those in the Protein Data Bank (PDB). Z-score is a standard score that is converted from an original score. The list of neighbours is sorted by Z-score. Similarities with a Z-score lower than 2 are spurious. RMSD(Root Mean Square Deviation) value is used to measure the degree to which atoms deviate from the alignment position.
| Named | CAS | Pubchem CID | Structure |
|---|---|---|---|
| 1IRL-A | 2.5 | 115 | Interleukin-2 |
| 2Z3R-E | 2.7 | 105 | Interleukin-15 |
| 1BBN-A | 2.6 | 108 | Interleukin-4 |
| 7OX6-A | 3.0 | 100 | Interleukin-9 |
| 6O4O-A | 3.3 | 99 | Interleukin-11 |
| 8D7H-D | 2.8 | 102 | Ciliary |
| 7CJN-B | 3.1 | 98 | Interleukin |
| 2L3Y-A | 2.8 | 96 | Interleukin-6 |
| 8DH9-D | 3.6 | 104 | Leptin |
| 1BUY-A | 3.2 | 109 | Protein |
References
[1] The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design.Waldmann T. A.
Nature reviews. Immunology, 6(8), 595–601. (2006)
[2] Interleukin-2 receptor signaling: at the interface between tolerance and immunity.
Malek, T. R., & Castro, I.
Immunity, 33(2), 153–165. (2010)
[3] Interleukin-2 functions in anaplastic large cell lymphoma cells through augmentation of extracellular signal-regulated kinases 1/2 activation.
Ito, M., Zhao, N., Zeng, Z., Zhou, X., Chang, C. C., & Zu, Y.
International journal of biomedical science : IJBS, 7(3), 181–190. (2011)
[4] Soluble IL-2Ralpha facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma.
Yang, Z. Z., Grote, D. M., Ziesmer, S. C., Manske, M. K., Witzig, T. E., Novak, A. J., & Ansell, S. M.
Blood, 118(10), 2809–2820. (2011)
[5] Induced and natural regulatory T cells in human cancer.
Whiteside TL, Schuler P, Schilling B.
Expert opinion on biological therapy, 12(10), 1383–1397. (2012)
[6] Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma.
Mir, M. A., Maurer, M. J., Ziesmer, S. C., Slager, S. L., Habermann, T., Macon, W. R., Link, B. K., Syrbu, S., Witzig, T., Friedberg, J. W., Press, O., LeBlanc, M., Cerhan, J. R., Novak, A., & Ansell, S. M.
Blood, 125(6), 992–998. (2015)
[7] Evolving synergistic combinations of targeted immunotherapies to combat cancer.
Melero, I., Berman, D. M., Aznar, M. A., Korman, A. J., Pérez Gracia, J. L., & Haanen, J.
Nature reviews. Cancer, 15(8), 457–472. (2015)
[8] Nucleic acid aptamers in cancer research, diagnosis and therapy.
Ma, H., Liu, J., Ali, M. M., Mahmood, M. A., Labanieh, L., Lu, M., Iqbal, S. M., Zhang, Q., Zhao, W., & Wan, Y.
Nucleic acid aptamers in cancer research, diagnosis and therapy. Chemical Society reviews, 44(5), 1240–1256. (2015)
[9] Associations between elevated pre-treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma.
Binder, M., O'Byrne, M. M., Maurer, M. J., Ansell, S., Feldman, A. L., Cerhan, J., Novak, A., Porrata, L. F., Markovic, S., Link, B. K., & Witzig, T. E.
American journal of hematology, 92(8), 752–758. (2017)
[10] An RNA Aptamer-Based Biomarker Platform Demonstrates High Soluble CD25 Occupancy by IL2 in the Serum of Follicular Lymphoma Patients.
Veeramani, S., Blackwell, S. E., Thiel, W. H., Yang, Z. Z., Ansell, S. M., Giangrande, P. H., & Weiner, G. J.
Cancer immunology research, 7(9), 1511–1522. (2019)