INTERLEUKIN-21 VARIANTS WITH ALTERED BINDING TO THE IL-21 RECEPTOR FIELD OF THE INVENTION The inventton Is concerned with new IL-21 variants having an altered binding to the common gamma chain (YC) and the use thereof in therapy. BACKGROUND OF THE INVENTION lnterleukin-21 (IL-21) is a recently identified type 1 cytokine, which is secreted as a 133-amino acid protein by activated CD4* T cells (Parrish-Novak.J. et al., Nature 408. 57-63 (2000)). The IL-21 cytokine has been demonstrated to possess potent stimulatory effects on the proliferation, differentiation and activation of several classes of haematopoietic cells including B-cells, T-cells and NK-cells. The biological effects of IL-21 are mediated via activation of the IL-21 receptor complex, which is composed of an IL-21 private receptor chain (IL-21 Ra) in complex with the common gamma chain (YO). which similarly constitutes an essential component of the signalling receptor complex of the cytokines IL-2, IL-4, lL-7, IL-9, and IL-15. These cytokines thus constitute a subfamily referred to as common gamma chain cytokines, with IL-21 being the most recently added member. Within the common gamma chain family of cytokines, high resolution structural information has been obtained through X-ray crystallography and NMR spectroscopy for IL-2 and IL-4 (Brandhuber.B.J. et al., Science 238.1707-1709 (1987), Mott,H.R. etal., Journal of Molecular Biology 247, 979-994 (1995), Powers,R. etal., Science 256,1673-1677 (1992), WIodaver,A. et al., Febs Letters 309, 59-64 (1992). It is apparent from these studies that IL-2 and IL-4 along v\nth other type 1 cytokines, including IL-ip, IL-2, IL-4, and GM-CSF, share a common overall topology in their structures in spite of a distant homology in primary sequence. The common structural motif of these proteins consists of a central four-helical bundle, an-anged in an up-up-down-down topology, connected by loops which are characterized by a high degree of structural freedom, a considerable difference in loop length, and variation in the number, and positioning, of stabilizing disulfide bridges. In the iL-21 amino acid sequence as shown in SEQ ID No. 1 (a 162 aa long polypeptide), helix A is defined by amino acid residues 41-56; helix B by amino acid residues 69-84 ; helix C by amino acid residues 92-105; and helix D by amino acid residues 135-148. Crystal structures have also been reported for IL-2 and IL-4 in complex with the corresponding private chains and, in the case of IL-2. the common gamma chain (Wang,X.Q. et al., Science 310,1159-1163 (2005), HageJ. et al.. Cell 97. 271-281 (1999)). IL-2 is distinct from both IL-4 and IL-21 by having two private receptor chains, IL-2Ra and IL-2RP, where iL-2Rp is homologous to iL-4Ra and iL-21Ra. Only minor structural differences are observed between the free and receptor bound forms of lL-2 and lL-4 indicating that only slight structural changes occur for these cytokines upon complex fomation. These studies accurately identify the residues of the cytol and determines their importance for YC binding by functional characterization of the corresponding individually alanine substituted IL-21 variants. A high-resolution three-dimensional structure of Met-hlL-21 (SEQ ID No.3, which is fragment 30-162 of SEQ ID No. 1 with an additional N-terminal methionine) was resolved by heteronudear NMR spectroscopy. Overall the Met-hlL-21 structure is dominated by a well-defined central four-helicat bundle, arranged in an up-up-down-down topology, as observed for other cytokines. A 30 model of the complex between IL-21 and Vc was created based on the crystal structure of the lL-2/Yc/IL-2Ra/IL-2Rp receptor complex together with the NMR structure of Met-hlL-21. Residues of IL-21 involved in YC binding were identified using the 3D model. For the set of residues in IL-21 involved in binding to YC. an alanine scan was canned out to detennine the importance of individual residues for YC binding. Knowledge of these individual residues is used in the generation of variants of IL-21 having a modulated binding to YC- For example abolishment of binding to Yc may lead to the generation of IL-21 variants with antagonistic properties as mentioned above, while IL-21 variants with improved binding to Yc may lead to superactive IL-21 agonists. The present invention concerns isolated IL-21 peptides having a mutation in one or more amino acid residues as compared to an IL-21 peptide having the amino acid sequence of SEQ ID No.2, wherein the activation mediated by said peptide through the IL-21 receptor is altered as compared to an IL-21 peptide having the amino acid sequence of SEQ ID No. 2. The present invention also concerns an isolated IL-21 peptide having a mutation in one or more of the amino acid residues involved in the binding of IL-21 to the common gamma chain (Vc) of the IL-21 receptor, wherein the activation mediated by said peptide through the IL-21 receptor is altered as compared to an IL-21 peptide having the amino acid sequence of SEQ ID No. 2. The activation mediated by said peptide may for instance be detemined by use of Assay (la) or (lb) herein. In one embodiment, the invention relates to an isolated lL-21 peptide having a mutation in one or more of the amino acid residues involved in the binding of IL-21 to the common gamma chain (YC) of the IL-21 receptor, wherein the IL-21 peptide has an altered binding to the IL-21 receptor as compared to an IL-21 peptide having the amino acid sequence of SEQ ID No. 2. The binding to the IL-21 peptide to the IL-21 receptor may for instance be determined by use of Assay (11) as described herein or may be measured indirectly by measuring the activivation as described in Assays (la) and (lb). In one embodiment, the invention relates to an isolated IL-21 peptide having a mutation in one or more of the amino acid residues involved in the binding of IL-21 to the common gamma chain (Vc) of the IL-21 receptor, wherein said IL-21 peptide has an altered binding to the Ve of the IL-21 receptor as compared to an IL-21 peptide having the amino acid sequence of SEQ ID No. 2. The binding to the IL-21 peptide to the IL-21 receptor or the common gamma chain (YC) may for instance be determined by use of Assay (II) as described herein. The term peptide includes any suitable peptide and may be used synonymously with the terms polypeptide and protein, unless otherwise stated or contradicted by context; provided that the reader recognize that each type of respective amino acid polymer-containing molecule may be associated with significant differences and thereby form individual embodiments of the present invention (for example, a peptide such as an antibody, which is composed of multiple polypeptide chains, is significantly different from, for example, a single chain antibody, a peptide immunoadhesin, or single chain immunogenic peptide). Therefore, the term peptide herein should generally be understood as referring to any suitable peptide of any suitable size and composition (with respect to the number of amino acids and number of associated chains in a protein molecule). IVIoreover, peptides in the context of the inventive methods and compositions described herein may comprise non-naturally occurring and/or non-L amino acid residues, unless otherwise stated or contradicted by context. The term peptide, unless othenwise stated or contradicted by context,(and if discussed as individual embodiments of the temi(s) polypeptide and/or protein) also encompasses derivatized peptide molecules. Briefly, In the context of the present invention, a derivative is a peptide in which one or more of the amino acid residues of the peptide have been chemically modified (for instance by alkylation, acylation, ester formation, or amide fomnation) or associated with one or more non-amino acid organic and/or inorganic atomic or molecular subslituents (for instance a polyethylene glycol (PEG) group, a lipophilic substituent (which optionally may be linked to the amino add sequence of the peptide by a spacer residue or group such as ^-alanine, y-aminobutyric acid (GABA), L/D-glutamic acid, succinic acid, and the tike), a fluorophore, biotin, a radionuclide, etc.) and may also or alternatively comprise non-essential, non-naturally occurring, and/or non-L amino acid residues, unless otherwise stated or contradicted by context (however, it should again be recognized that such derivatives may, in and of themselves, be considered independent features of the present invention and inclusioii of such molecules within the meaning of peptide is done for the sake of convenience in describing the present invention rather than to imply any sort of equivalence between naked peptides and such derivatives). Non-limiting examples of such amino acid residues include for instance 2-aminoadipic acid, 3-amino-adipic acid, p-alanine, p-aminopropionic acid, 2-aminobutyric acid, 4-aminobutyric acid, 6-aminocaproic acid, 2-aminoheptanoic acid, 2-aminoisobutyric acid, 3-aminoisobutyric acid, 2-aminopimelic acid, 2,4-diaminobutyric acid, desmosine, 2,2'-diaminopimelic acid, 2,3-di-aminopropionic acid, N-ethylglycine, N-ethylasparagine, hydroxyiysine, allohydroxylysine, 3-hydroxyproline, 4-hydroxyproline, isodesmosine, alloisoleucine, N-methylglycine, N-methyl-isoleucine, 6-N-methyllysine, N-methylvaline, non^aline, norleucine, ornithine, and statine halogenated amino acids. IL-21 peptides refers to any peptide that specifically binds to the IL-21 receptor under cellular and/or physiological conditions for an amount of time sufficient to induce, promote, enhance, and/or othenwise modulate a physiological effect associated with the antigen; to allow detection by ELISA, Western blot, or other similarly suitable protein binding technique described herein and/or known In the art and/or to otherwise be detectably bound thereto after a relevant period of time (for instance at least about 15 minutes, at least about 30 minutes, at least about 45 minutes, at least about 1 hour, at least about 2 hours, at least about 4 hours, at least about 6 hours, at least about 12 hours, about 1-24 hours, about 1-36 hours, about 1-48 hours, about 1-72 hours, about one week, or longer). The binding of the IL-21 peptide to the IL-21 receptor may for instance be determined by use of Assay (II) as described herein or may be measured indirectly by measuring the activivation as described in Assays (la) and (lb). In one embodiment, a IL-21 peptide according to the present invention is an analogue of human IL-21. The term "analogue" as used herein referring to a polypeptide means a modified peptide wherein one or more amino acid residues of the peptide have been substituted by other amino acid residues and/or wherein one or more amino acid residues have been deleted from the peptide and or wherein one or more amino acid residues have been added to the peptide. Such addition or deletion of amino acid residues can take place at the N- tenninal of the peptide and/or at the C-tenninal of the peptide and/or in-chain. All amino acids for which the optica! isomer is not stated are to be understood to mean the L-isomer. The term "IL-21 analogue" or "analogue of IL-21" or "analogue of human IL-21"as used herein referring to an analogue of IL-21 (or human IL-21), which has the capability of binding to the IL-21 receptor and in particular to the common gamma chain (YC) of the IL-21 receptor. sn one embodiment, an IL-21 peptide of the invention has an amino acid sequence, having at least 80% identity to SEQ ID No. 1 or SEQ ID No. 2. In one embodiment, an IL-2.1 peptide of the invention has an amino acid sequence having at least 85%, such as at least 90%, for instance at least 95%, such as for instance at least 99% identity to SEQ ID No. 1 or SEQ ID No. 2. The temn "identity" as le signal peptide may conveniently be derived from a gene encoding an Aspergillus sp, amylase or glucoamylase, a gene encoding a Rhizomucor miehei lipase or protease or a Humicola lanuginosa lipase. The signal peptide may be derived from a gene encoding A. oryzae TAKA amylase, A. niger neutral a-amylase, A. niger acid-stable amylase, or A. n/ger glucoamylase. The procedures used to ligate the DNA sequences coding for the present peptide, the promoter and optionally the terminator and/or secretory signal sequence, respectively, and to insert them into suitable vectors containing the Information necessary for replication, are well known to persons skilled in the art (cf., for instance, Sambrook et al., op.cit.). The host cell into which the DNA construct or the recombinant vector of the invention is introduced may be any cell which is capable of producing the present peptide and includes bacteria, yeast, fungi and higher eukaryotic cells. The present invention also related to a host cell comprising a nucleic acid construct according to the present invention, or a vector according to the present invention. Examples of bacterial host cells which, on cultivation, are capable of producing the peptide of the invention are grampositive bacteria such as strains of Bacillus, such as strains of S. subtilis, B. licheniformis, B. lentus, B. brevis, B. stearothermophilus, B. alkalophilus, B. amyloliquefaciens, B. coagulans, B. circulans, B. lautus, B. megatherium or 13. thuringiensis, or strains of Streptomyces, such as S. lividans or S. murinus, or gram negative bacteria such as Echerichia coll. The transfomiation of the bacteria may be effected by protoplast transfomiation or by using competent cells in a manner known per se (cf. Sambrook et al., supra). Other suitable hosts include S. mobaraense, S. lividans, and C. glutamicum (Appl. Microbiol. Biotechnol. 64. 447-454 (2004)). When expressing the peptide in bacteria such as E. coli, the peptide may be retained in the cytoplasm, typically as insoluble granules (known as inclusion bodies), or may be directed to the periplasmic space by a bacterial secretion sequence. In the fonner case, the cells are lysed and the granules are recovered and denatured after which the peptide is refolded by diluting the denaturing agent. In the latter case, the peptide may be recovered from the periplasmic space by disrupting the cells, e.g. by sonication or osmotic shock, to release the contents of the periplasmic space and recovering the peptide. Examples of suitable yeasts cells include cells of Saccharomyces spp. or Schizosaccharomyces spp., in particular strains of Saccharomyces cerevisiae or Saccharomyces kluyveri. Methods for transforming yeast cells WAh heterologous DNA and producing heterologous proteins therefrom are described, e.g. in US 4,599,311, US 4 031,373, US 4,870,008, 5,037,743, and US 4.845,075, all of v»/hich are hereby incorporated by reference. Transformed cells are selected by a phenotype detemiined by a selectable marker, commonly drug resistance or the ability to grow in the absence of a particular nutrient, e.g. leucine. An example of a vector for use in yeast is the P0T1 vector disclosed in US 4,931,373. The DNA sequence encoding the peptide of the invention may be preceded by a signal sequence and optionally a leader sequence , e.g. as described above. Further examples of suitable yeast cells are strains of Kluyveromyces, such as K. lactis, Hansenula, e.g. H. polymorpha, or PIchIa, e.g. P. pastoris (cf. Gleeson et ai., J. Gen. IVIicrobiol. 132, 3459-3465 (1986); US 4.882,279). Examples of other fungal cells are cells of filamentous fungi, e.g. Aspergillus spp., Neurospora spp., Fusarlum spp. or Trichoderma spp., in particular strains of A. oryzae, A. nidulans or A. niger. The use of Aspergillus spp. for the expression of proteins is described in, e.g., EP 272 277 and EP 230 023. The transformation of F. oxysporum may, for instance, be earned out as described by Malardier et al. Gene 78,147-156 (1989). When a filamentous fungus is used as the host cell, it may be transformed with the DNA construct of the invention, conveniently by integrating the DNA construct in the host chromosome to obtain a recombinant host cell. This will make it more likely that the DNA sequence will be stably maintained in the cell. Integration of the DNA constructs into the host chromosome may be performed according to conventional methods, e.g. by homologous or heterologous recombination. The transformed or transfected host cell described above is then cultured in a suitable nutrient medium under conditions permitting the expression of the present peptide, after which the resulting peptide is recovered from the culture. The medium used to culture the cells may be any conventional medium suitable for growing the host ceils, such as minima! or complex media containing appropriate supplements. Suitable media are available from commercial suppliers or may be prepared according to published recipes (e.g. in catalogues of the American Type Culture Collection). The peptide produced by the cells may then be recovered from the culture medium by conventional procedures including separating the host cells from the medium by centrifugation or filtration, precipitating the proteinaceous components of the supernatant or filtrate by means of a salt, e.g. ammonium sulphate, purification by a variety of chromatographic procedures, e.g. ion exchange chromatography, gelfiltration chromatography, affinity chromatography, or the iil95%. NMR experiments Unless othenvise specified, NMR spectra were acquired at 27''C on a Bruker Avance 600 MHz spectrometer equipped with a 5mm ''H {^®N, ^^C} TXI probe. 1D ''H spectra were acquired for Met-hlL-21 samples with concentrations in the range 0.2-2.0 mM. Sequential backbone assignments were done using established methods as described in Yamazakl,T. et al., Joumal of the American Chemical Society 116,11655-11666 (1994) and Hyberts.S.G. et al., Journal of Biomolecular NMR 26, 335-344 (2003). Assignment of side chain resonances included use of HN(CO)HAHB, H(C)(CCCO)NH, (H)C(CCCO)NH, H(C)CH-TOCSY and (H)CCH-TOCSY spectra as well as '^N- and "C-edited NOESY-HSQC spectra. The ^^N- and ^^C-edited NOESY-HSQC spectra were acquired on a Varian Inova 800 MHz spectrometer equipped with a 3mm triple resonance probe and on a Bruker Avance 600 MHz spectrometer equipped with a 5mm ^H {^^N, "0} TXI cryoprobe, respectively. Temperature studies were performed by acquiring ^^N-HSQC spectra at temperatures between 10 and 50°C. Control spectra at ZTC were acquired before and after the experiments. "N-HSQC type exchange experiments were acquired with mixing times ranging from 0 to 1000 ms, Experiments measuring backbone amide "N T, and T2 relaxation times and heteronuclear {^H}-'"'N NOEs were acquired on a Bruker Avance 600MHz spectrometer equipped with a 5mm ''H {^®N, ^^0} TXI cryoprobe. Ti and T2 values were detemnined by least-square fitting of signal intensities to an exponential curve. Heteronuclear {^H^"N NOEs were calculated as the intensity ratios between ^®N-HSQC spectra recorded with and without proton saturation. Resolution of the Met'lilL-21 structure by NMR The "N HSQC spectra recorded for Met-hlL-21 display a fairly good dispersion despite a number of signals at random coil chemical shift values. These latter signals are due to the presence of flexible regions in the Met-hlL-21 molecule. Dilution experiments reveal no signs of aggregation in the range of 0.2-2.0 mM Met-hlL-21. Only minor changes were observed in ^^N HSQC spectra acquired at different pH values and salt concentrations (pH between 5.0-7.0 and NaCI between 0-100mM). Bacl0.5A 0 Dihedral-angle constraint violations per CYANA confonne > 5 degrees 0.2 ^Each disulfid bond is constrained bv three upper and thre ie lower bounds. Example 2 Determining the amino acid residues in IL-21 involved in the binding to Vn Resonances were assigned using a standard set of three-dimensional experiments (Y;imazal