View source for IL2RA

{{Short description|Mammalian protein found in Homo sapiens}}
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{{Redirect-distinguish|CD25|Cdc25}}
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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 [[Pleiotropy|pleiotropic]] [[cytokine]] which plays an important role in immune [[homeostasis]].<ref name=":1">{{cite journal | vauthors = Spolski R, Li P, Leonard WJ | title = Biology and regulation of IL-2: from molecular mechanisms to human therapy | journal = Nature Reviews. Immunology | volume = 18 | issue = 10 | pages = 648–659 | date = October 2018 | pmid = 30089912 | doi = 10.1038/s41577-018-0046-y | s2cid = 51939991 }}</ref><ref name=":5">{{cite journal | vauthors = Zhou P | title = Emerging mechanisms and applications of low-dose IL-2 therapy in autoimmunity | journal = Cytokine & Growth Factor Reviews | volume = 67 | pages = 80–88 | date = October 2022 | pmid = 35803833 | doi = 10.1016/j.cytogfr.2022.06.003 | s2cid = 250200065 | doi-access = free }}</ref>

== Genetics ==
The human [[protein]] interleukin-2 receptor subunit alpha is encoded by a [[gene]] called ''IL2RA'' with a length around 51,6 kb. Alternative names for this protein coding gene are ''IL2R'', ''IDDM10'' and ''TCGFR''. Location of ''IL2RA'' in human [[genome]] is on the short arm of 10th chromosome (10p15.1).<ref name="pmid3925551">{{cite journal | vauthors = Leonard WJ, Donlon TA, Lebo RV, Greene WC | title = Localization of the gene encoding the human interleukin-2 receptor on chromosome 10 | journal = Science | volume = 228 | issue = 4707 | pages = 1547–1549 | date = June 1985 | pmid = 3925551 | doi = 10.1126/science.3925551 | bibcode = 1985Sci...228.1547L }}</ref><ref name=":2">{{Cite web |title=IL2RA Gene - GeneCards {{!}} IL2RA Protein {{!}} IL2RA Antibody |url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=IL2RA |access-date=2023-01-25 |website=www.genecards.org}}</ref><ref name=":3">{{Cite web |title=UniProt |url=https://www.uniprot.org/uniprotkb/P01590/entry |access-date=2023-01-25 |website=www.uniprot.org}}</ref>

Several frequent point [[mutation]]s, [[Single-nucleotide polymorphism|single nucleotide polymorphism]] (SNP), have been identified in or in close proximity to ''IL2RA'' gene in the population. These SNPs have been linked mainly to susceptibility to immune dysregulation disorders, with majority found in research on [[multiple sclerosis]] (MS) and [[Type 1 diabetes|type 1 diabetes mellitus]].<ref>{{cite journal | vauthors = Buhelt S, Søndergaard HB, Oturai A, Ullum H, von Essen MR, Sellebjerg F | title = Relationship between Multiple Sclerosis-Associated ''IL2RA'' Risk Allele Variants and Circulating T Cell Phenotypes in Healthy Genotype-Selected Controls | journal = Cells | volume = 8 | issue = 6 | pages = 634 | date = June 2019 | pmid = 31242590 | pmc = 6628508 | doi = 10.3390/cells8060634 | doi-access = free }}</ref><ref>{{Cite journal | vauthors = Pourakbari R, Hosseini M, Aslani S, Ayoubi-joshaghani MH, Valizadeh H, Roshangar L, Ahmadi M, Shirvani B |date=September 2020 |title=Association between interleukin 2 receptor A gene polymorphisms (rs2104286 and rs12722489) with susceptibility to multiple sclerosis in Iranian population |journal=Meta Gene |language=en |volume=25 |pages=100750 |doi=10.1016/j.mgene.2020.100750}}</ref><ref>{{cite journal | vauthors = Qu HQ, Montpetit A, Ge B, Hudson TJ, Polychronakos C | title = Toward further mapping of the association between the IL2RA locus and type 1 diabetes | journal = Diabetes | volume = 56 | issue = 4 | pages = 1174–1176 | date = April 2007 | pmid = 17395754 | doi = 10.2337/db06-1555 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Qu HQ, Bradfield JP, Bélisle A, Grant SF, Hakonarson H, Polychronakos C | title = The type I diabetes association of the IL2RA locus | journal = Genes and Immunity | volume = 10 | issue = Suppl 1 | pages = S42–S48 | date = December 2009 | pmid = 19956099 | pmc = 2805446 | doi = 10.1038/gene.2009.90 }}</ref><ref>{{cite journal | vauthors = Lowe CE, Cooper JD, Brusko T, Walker NM, Smyth DJ, Bailey R, Bourget K, Plagnol V, Field S, Atkinson M, Clayton DG, Wicker LS, Todd JA | title = Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes | journal = Nature Genetics | volume = 39 | issue = 9 | pages = 1074–1082 | date = September 2007 | pmid = 17676041 | doi = 10.1038/ng2102 | s2cid = 13940200 }}</ref>

''IL2RA'' gene [[orthologues]] with identical protein functionality are relatively abundant and constant among animal species, especially in [[mammal]]s subgroups. Moreover, conserved homologs of this gene are in mouse, rat, dog, cow, chimpanzee and Rhesus monkey.<ref>{{Cite web |title=Gene: IL2RA (ENSG00000134460) - Orthologues - Homo_sapiens - Ensembl genome browser 108 |url=http://www.ensembl.org/Homo_sapiens/Gene/Compara_Ortholog?db=core;g=ENSG00000134460;r=10:6010689-6062370 |access-date=2023-01-25 |website=www.ensembl.org}}</ref><ref>{{Cite web |title=IL2RA interleukin 2 receptor subunit alpha [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/3559 |access-date=2023-01-25 |website=www.ncbi.nlm.nih.gov |language=en}}</ref>

== Expression ==
CD25 is expressed broadly among [[White blood cell|leukocytes]]. The highest surface expression of this protein is on [[Regulatory T cell|regulatory T cells (Tregs)]], where CD25 is expressed constitutively, especially on a subset classified as naturally occurring Tregs. It can also be found on activated [[B cells]], [[Natural killer cell|NK (natural killer) cells]], [[thymocytes]], and some [[Myeloblast|myeloid]] lineage cells (e.g. [[macrophage]]s, [[dendritic cell]]s).<ref>{{cite journal | vauthors = Abel AM, Yang C, Thakar MS, Malarkannan S | title = Natural Killer Cells: Development, Maturation, and Clinical Utilization | journal = Frontiers in Immunology | volume = 9 | pages = 1869 | date = 2018-08-13 | pmid = 30150991 | pmc = 6099181 | doi = 10.3389/fimmu.2018.01869 | doi-access = free }}</ref><ref name=":4">{{cite journal | vauthors = Li Y, Li X, Geng X, Zhao H | title = The IL-2A receptor pathway and its role in lymphocyte differentiation and function | journal = Cytokine & Growth Factor Reviews | volume = 67 | pages = 66–79 | date = October 2022 | pmid = 35803834 | doi = 10.1016/j.cytogfr.2022.06.004 | s2cid = 250252097 }}</ref> ''IL2RA'' has been used as a marker to identify CD4+FoxP3+ [[regulatory T cell]]s in mice. However, there are species differences as CD25 is constitutively expressed by a large proportion of resting [[memory T cell]]s non-regulatory CD4 T cells in humans that are absent in mice.<ref>{{cite journal | vauthors = Triplett TA, Curti BD, Bonafede PR, Miller WL, Walker EB, Weinberg AD | title = Defining a functionally distinct subset of human memory CD4+ T cells that are CD25POS and FOXP3NEG | journal = European Journal of Immunology | volume = 42 | issue = 7 | pages = 1893–1905 | date = July 2012 | pmid = 22585674 | doi = 10.1002/eji.201242444 }}</ref><ref>{{cite journal | vauthors = El-Maraghy N, Ghaly MS, Dessouki O, Nasef SI, Metwally L | title = CD4+CD25-Foxp3+ T cells as a marker of disease activity and organ damage in systemic lupus erythematosus patients | journal = Archives of Medical Science | volume = 14 | issue = 5 | pages = 1033–1040 | date = August 2018 | pmid = 30154885 | pmc = 6111364 | doi = 10.5114/aoms.2016.63597 }}</ref> High expression of CD25 is also found on [[T-cell receptor|TCR]] activated conventional T cells (both [[Cytotoxic T cell|CD8+]] and [[T helper cell|CD4+]] T lymphocytes), where it is considered to be a marker of T cell activation.<ref>{{cite journal | vauthors = Shipkova M, Wieland E | title = Surface markers of lymphocyte activation and markers of cell proliferation | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 413 | issue = 17–18 | pages = 1338–1349 | date = September 2012 | pmid = 22120733 | doi = 10.1016/j.cca.2011.11.006 }}</ref> Additionally, expression of the IL-2 receptor alpha subunit can be found in non-lymphoid tissues such as lungs ([[alveolar macrophage]]s), liver ([[Kupffer cell]]s) and skin ([[Langerhans cell]]s).<ref name=":1" /><ref name=":4" />

''IL2RA'' protein can be expressed in many types of [[neoplastic cells]], such as in most B-cell neoplasms, T-cell [[lymphoma]]s, some acute nonlymphocytic [[leukemias]], [[neuroblastoma]]s, [[mastocytosis]], [[Waldenström macroglobulinemia|Waldenstrom macroglobuliaemia]] and [[tumor infiltrating lymphocyte]]s.<ref>{{cite journal | vauthors = Flynn MJ, Hartley JA | title = The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer | journal = British Journal of Haematology | volume = 179 | issue = 1 | pages = 20–35 | date = October 2017 | pmid = 28556984 | doi = 10.1111/bjh.14770 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Jones D, Ibrahim S, Patel K, Luthra R, Duvic M, Medeiros LJ | title = Degree of CD25 expression in T-cell lymphoma is dependent on tissue site: implications for targeted therapy | journal = Clinical Cancer Research | volume = 10 | issue = 16 | pages = 5587–5594 | date = August 2004 | pmid = 15328201 | doi = 10.1158/1078-0432.CCR-0721-03 | doi-access = free }}</ref>

== Structure ==
Interleukin-2 receptor alpha chain is an [[Integral membrane protein|integral-membrane protein]], more precisely [[type I transmembrane protein]]. This bitopic polypeptide is constructed by a sequence of 272 [[amino acid]]s and has a molecular mass of around 30.8 kDa.<ref name=":2" /> CD25 consists of three domains: extracellular (N-terminus), transmembrane (alpha-helix) and cytoplasmic (C-terminus). However, while extracellular part is able to function as a [[binding site]] for [[Interleukin 2|interleukin-2]], short cytoplasmic domain lacks an ability to induce [[Intracellular signalling pathways|intracellular signalling]] and therefore needs to oligomerise with other IL-2 receptor subunits.<ref name=":2" /><ref name=":3" /> The [[Interleukin 2|interleukin-2]] (IL2) receptor alpha (''IL2RA'') and beta (''[[IL2RB]])'' chains, together with the common gamma chain (''[[IL2RG]]''), constitute the high-affinity IL-2 receptor complex (''K''d ~10−11M). Homodimeric alpha chains (''IL2RA'') result in low-affinity receptor (''K''d ~10−8M) with no signalling ability, while dimeric beta (''[[IL2RB]]'') and gamma chains (''[[IL2RG]]'') produce a medium-affinity receptor (''K''d ~10−9M). Moreover, CD25 is an exclusive subunit that entirely binds IL-2, while CD132 binds the shared γc family cytokines ([[Interleukin 4|IL-4]], [[Interleukin 7|IL-7]], [[Interleukin 9|IL-9]], [[Interleukin 15|IL-15]] and [[Interleukin 21|IL-21]]), and the CD122 subunit binds also [[Interleukin 15|IL-15]].<ref name=":1" /><ref name=":0">{{cite journal | vauthors = Goudy K, Aydin D, Barzaghi F, Gambineri E, Vignoli M, Ciullini Mannurita S, Doglioni C, Ponzoni M, Cicalese MP, Assanelli A, Tommasini A, Brigida I, Dellepiane RM, Martino S, Olek S, Aiuti A, Ciceri F, Roncarolo MG, Bacchetta R | title = Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity | journal = Clinical Immunology | volume = 146 | issue = 3 | pages = 248–261 | date = March 2013 | pmid = 23416241 | pmc = 3594590 | doi = 10.1016/j.clim.2013.01.004 }}</ref><ref name=":6" />

Soluble ''IL2RA'' has been isolated and determined to result from extracellular [[proteolysis]] during activation of T lymphocytes.<ref name=":4" /> Also, alternately-spliced ''IL2RA'' [[Messenger RNA|mRNAs]] have been isolated, but the significance of each is currently unknown.<ref>{{cite web |title=Entrez Gene: IL2RA interleukin 2 receptor, alpha |url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3559}}</ref>

== Signalling cascade of interleukin-2 Receptor ==
Interleukin-2 can interact with intermediate-affinity dimeric IL-2 receptor, which consists of beta ([[IL2RB|CD122]]) and gamma ([[Common gamma chain|CD132]]) chains or with high-affinity trimeric complex, where also alpha subunit (CD25) constructs the IL-2 receptor and provides enhanced specific binding force. After activation of the receptor by its [[ligand]], [[Heterodimerization|heterodimerisation]] of beta and gamma intracellular domains takes place.<ref name=":1" /><ref name=":0" /> This coupling of subunits brings together [[Janus kinase]]s [[Janus kinase 1|JAK1]] and [[Janus kinase 3|JAK3]], considering their association with respective cytoplasmic parts of beta and gamma subunits. Downstream [[phosphorylation]] leads to initiation of three signalling pathways: [[JAK-STAT signaling pathway|JAK-STAT pathway]], [[PI3K/AKT/mTOR pathway|PI3K/Akt/mTOR pathway]] and [[MAPK/ERK pathway|Ras/Raf/MEK/ERK (MAPK) pathway]]. Regarding JAK-STAT pathway, particular [[STAT protein|signal transducers and activators of transcription]] participate in this signalling cascade: [[STAT5]], [[STAT1]] and [[STAT3]] and after [[Dimer (chemistry)|dimerisation]], they translocate to nucleus to perform [[transcription factor]] functions. All three signalling pathways are important for diverse cellular regulations, in terms of increased survival (anti-[[Apoptosis|apoptotic]] effect), proliferation and [[cell growth]], transcriptional regulation and [[Cellular differentiation|cell differentiation]].<ref name=":6">{{cite journal | vauthors = Peerlings D, Mimpen M, Damoiseaux J | title = The IL-2 - IL-2 receptor pathway: Key to understanding multiple sclerosis | journal = Journal of Translational Autoimmunity | volume = 4 | pages = 100123 | date = 2021 | pmid = 35005590 | pmc = 8716671 | doi = 10.1016/j.jtauto.2021.100123 }}</ref><ref name=":5" /> T lymphocytes are influenced by IL-2R signalling in case of [[T helper cell|CD4+ T helper]] subtype differentiation: promoting [[Th1 cell|Th1]], [[Th2]], [[Th 9 cell|Th9]], Tfr (T follicular regulatory cells) and suppressing [[T helper 17 cell|Th17]], Tfh ( T follicular helper cells). Additionally, strength of IL-2R signalling in [[Cytotoxic T cell|CD8+ T cytotoxic lymphocytes]] may be connected to phenotypic fate of these cells for effector and memory T cells formation.<ref name=":1" /><ref name=":4" /><ref>{{cite journal | vauthors = Kalia V, Sarkar S | title = Regulation of Effector and Memory CD8 T Cell Differentiation by IL-2-A Balancing Act | journal = Frontiers in Immunology | volume = 9 | pages = 2987 | date = 2018-12-20 | pmid = 30619342 | doi = 10.3389/fimmu.2018.02987 | pmc = 6306427 | doi-access = free }}</ref>

==Clinical significance==
Roifman's group was the first to identify immunological consequences of CD25 loss and the patient has suffered from [[chronic infection]]s and severe [[autoimmunity]] resembling Immune dysregulation, [[Autoimmune polyendocrine syndrome|Polyendocrinopathy]], Enteropathy X-linked ([[IPEX syndrome|IPEX]]) syndrome, caused by mutations in [[FOXP3]] gene.<ref name=":0" />

=== CD25 as a biomarker ===
Levels of CD25 soluble form, called ''sIL-2Rα'', has been connected to pathogenesis of [[autoimmune disease]]s and [[cancer]]. Since sCD25 is produced during immune activation, it is used as one of [[biomarker]]s to track disease progression and to indicate outcome for clinical disorders. Especially, it is a hallmark for hyper-activated immune system and [[cytokine storm]], which may lead to multiple organ system failure.<ref name=":7">{{cite journal | vauthors = Damoiseaux J | title = The IL-2 - IL-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor | journal = Clinical Immunology | volume = 218 | pages = 108515 | date = September 2020 | pmid = 32619646 | doi = 10.1016/j.clim.2020.108515 | doi-access = free }}</ref> In cancer, increased levels of this soluble protein are diagnostic marker for [[leukemia]] and [[lymphoma]].<ref>{{cite journal | vauthors = Janik JE, Morris JC, Pittaluga S, McDonald K, Raffeld M, Jaffe ES, Grant N, Gutierrez M, Waldmann TA, Wilson WH | title = Elevated serum-soluble interleukin-2 receptor levels in patients with anaplastic large cell lymphoma | journal = Blood | volume = 104 | issue = 10 | pages = 3355–3357 | date = November 2004 | pmid = 15205267 | doi = 10.1182/blood-2003-11-3922 | doi-access = free }}</ref> Furthermore, ''sIL-2Rα'' levels have some significance also in [[Infection|infectious diseases]] and [[Organ transplantation|transplantation]]. Higher serum levels were correlated with severity and need for hospitalisation of [[COVID-19]] patients.<ref>{{cite journal | vauthors = Kaya H, Kaji M, Usuda D | title = Soluble interleukin-2 receptor levels on admission associated with mortality in coronavirus disease 2019 | journal = International Journal of Infectious Diseases | volume = 105 | pages = 522–524 | date = April 2021 | pmid = 33711520 | pmc = 7942057 | doi = 10.1016/j.ijid.2021.03.011 }}</ref> ''sIL-2Rα'' amount in plasma of [[HIV|HIV ( human immunodeficiency virus)]] positive patients has a correlation to HIV viral load and so to disease progression. Similarly in [[Chagas disease]], caused by the [[protozoan]] ''[[Trypanosoma cruzi]],'' patients have increased levels of ''sIL-2Rα'' and [[Autoantibody|autoantibodies]].<ref>{{cite journal | vauthors = Mengel J, Cardillo F, Pontes-de-Carvalho L | title = Chronic Chagas' Disease: Targeting the Interleukin-2 Axis and Regulatory T Cells in a Condition for Which There Is No Treatment | journal = Frontiers in Microbiology | volume = 7 | pages = 675 | date = 2016-05-13 | pmid = 27242702 | pmc = 4866556 | doi = 10.3389/fmicb.2016.00675 | doi-access = free }}</ref> In regard to [[Organ transplantation|transplantation]], higher levels of sCD25 may be used as a predictor of organ rejection and [[Graft-versus-host disease|graft-versus-host disease (GVHD)]] for [[Hematopoietic stem cell transplantation|hematopoietic transplantations]]. Concerning [[Cardiovascular disease|CVD (cardiovascular diseases)]] soluble ''IL-2Rα'' has positive correlation with [[hypertension]], [[Type 2 diabetes|type 2 diabetes mellitus]], [[Sarcoidosis|cardiac sarcoidosis]], [[stroke]] and [[heart failure]]. For neurological disorders, high levels of ''sIL-2Rα'' are a sign for increased risk of developing [[schizophrenia]].<ref name=":4" />

=== CD25 as a therapeutic target ===
Since [[Regulatory T cell|Tregs]] express ''IL-2Rα'' subunit constitutively on the surface, some immunotherapeutic approaches try to use this information for selectivity.<ref name=":7" /> NARA1 [[antibody]] is used in antitumour approaches to preferentially supplement interleukin-2 to conventional [[Cytotoxic T cell|CD8+ T cells]] . NARA1 binds to the cytokine on the ''IL-2Rα'' [[binding site]] preventing binding to CD25. This complex should therefore interact with conventional T lymphocytes over T regulatory cells and thus increase [[Cytotoxicity|cytotoxic]] activity without increasing suppressing activity in tumour environment.<ref>{{cite journal | vauthors = Sahin D, Arenas-Ramirez N, Rath M, Karakus U, Hümbelin M, van Gogh M, Borsig L, Boyman O | title = An IL-2-grafted antibody immunotherapy with potent efficacy against metastatic cancer | journal = Nature Communications | volume = 11 | issue = 1 | pages = 6440 | date = December 2020 | pmid = 33353953 | pmc = 7755894 | doi = 10.1038/s41467-020-20220-1 | bibcode = 2020NatCo..11.6440S }}</ref> Antibodies directly against CD25 have been altered to contain  ‘activating’ [[Fc regions]] for the purpose of [[Antibody-dependent cellular cytotoxicity|antibody-dependent cell-mediated cytotoxicity]], in this case Treg depletion. Antibody marks a cell with ''IL-2Rα'' subunit on the surface, which is subsequently recognized and cleared by [[Myelocyte|myeloid cell]] with [[Fc receptor]].<ref name=":1" /> Moreover, for treatment of [[multiple sclerosis]], drug called [[daclizumab]] binds to ''IL2RA'' and so blocks high-affinity IL-2 receptors on recently activated T cells for interaction with IL-2 as well as IL-2 [[cross-presentation]] by [[dendritic cell]]s.<ref>{{cite web |year=2016 |title=Zinbryta Summary of Product Characteristics |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003862/WC500210598.pdf |publisher=European Medicines Agency |access-date=2016-12-09 |archive-date=2018-06-14 |archive-url=https://web.archive.org/web/20180614150719/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003862/WC500210598.pdf |url-status=dead }}</ref><ref>{{cite journal | vauthors = Pfender N, Martin R | title = Daclizumab (anti-CD25) in multiple sclerosis | journal = Experimental Neurology | volume = 262 | issue = Pt A | pages = 44–51 | date = December 2014 | pmid = 24768797 | doi = 10.1016/j.expneurol.2014.04.015 | s2cid = 32444028 | url = https://www.zora.uzh.ch/id/eprint/95741/1/pfender-martin-daclizumab-review-final-figures_included.pdf }}</ref>

From the other side, treatment strategies for [[Autoimmunity|autoimmune]] and [[Inflammation|inflammatory]] diseases need selectivity for [[Regulatory T cell|Tregs]] and suppression of immune system. ''IL-2Rα'' subunit expression on Tregs secures better sensitivity to [[Interleukin 2|IL-2]]. Therefore, administration of low doses of the cytokine preferentially stimulates T regulatory cells over others. Low-dose IL-2 therapy is used for [[graft-versus-host disease]], [[Type 1 diabetes|type 1 diabetes mellitus]], [[hepatitis C]] virus-induced [[vasculitis]] and [[systemic lupus]].<ref name=":1" /><ref name=":5" />

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Kuziel WA, Greene WC | title = Interleukin-2 and the IL-2 receptor: new insights into structure and function | journal = The Journal of Investigative Dermatology | volume = 94 | issue = 6 Suppl | pages = 27S–32S | date = June 1990 | pmid = 1693645 | doi = 10.1111/1523-1747.ep12875017 | doi-access = free }}
* {{cite journal | vauthors = Waldmann TA | title = The interleukin-2 receptor | journal = The Journal of Biological Chemistry | volume = 266 | issue = 5 | pages = 2681–2684 | date = February 1991 | pmid = 1993646 | doi = 10.1016/S0021-9258(18)49895-X | doi-access = free }}
* {{cite journal | vauthors = Vincenti F | title = Interleukin-2 receptor antagonists and aggressive steroid minimization strategies for kidney transplant patients | journal = Transplant International | volume = 17 | issue = 8 | pages = 395–401 | date = September 2004 | pmid = 15365604 | doi = 10.1007/s00147-004-0750-3 | s2cid = 9244114 | doi-access = free }}
{{refend}}

== External links ==
* [http://www.ebioscience.com/resources/mouse-cd-chart.htm Mouse CD Antigen Chart]
* [http://www.ebioscience.com/resources/human-cd-chart.htm Human CD Antigen Chart]
* [http://www3.interscience.wiley.com/cgi-bin/fulltext/114125497/HTMLSTART CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo]{{dead link|date=January 2025|bot=medic}}{{cbignore|bot=medic}}
* {{PDBe-KB2|P01589|Interleukin-2 receptor subunit alpha}}

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{{Cytokine receptors}}
{{Clusters of differentiation}}
{{Interleukin receptor modulators}}

[[Category:Clusters of differentiation]]