# Patent

## Title
MHC molecule-binding tumor-associated peptides

## Abstract

The invention relates to a tumor-associated peptide with an amino acid sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 577 from the attached sequence protocol, the peptide being capable of binding to a molecule of the human major histocompatibility complex (MHC) class I. The invention further relates to the use of the peptides for preparation of a drug and for the treatment of tumor diseases and/or adenomatous diseases. Furthermore, a pharmaceutical composition is described comprising at least one of the peptides.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a divisional of U.S. patent application Ser. No. 11/596,802, now U.S. Pat. No. 8,008,431, issued Aug. 30, 2011, filed Nov. 17, 2006, which is the U.S. National Stage of International Application No. PCT/EP2005/005619, filed May 24, 2005, which in turn claims priority to German Patent Application No. 10 2004 026 135.0, filed May 25, 2004. The contents of all applications are incorporated in their entirety by reference.


BACKGROUND
The present invention relates to tumor-associated peptides that are capable of binding to a molecule of the human class I major histocompatibility complex (MHC). Such peptides are, for example, used in the immunotherapy of tumor diseases.
The recognition of tumor-associated antigens (TAA) by immune system components plays a major role in the elimination of tumor cells by the immune system. This mechanism is based on the prerequisite that there are qualitative or quantitative differences between tumor cells and normal cells. In order to achieve an anti-tumor response, the tumor cells have to express antigens that are targets of an immune response sufficient for elimination of the tumor.
Particularly CD8-expressing cytotoxic T lymphocytes (in the following termed CTL) participate in tumor rejection. In order to elicit such an immune reaction by cytotoxic T cells, foreign proteins/peptides must be presented to the T cells. T cells recognize antigens as peptide fragments only if those are presented on cell surfaces by MHC molecules. These MHC (“major histocompatibility complex”) molecules are peptide receptors that normally bind peptides within the cell in order to transport them to the cell surface. This peptide/MHC molecule complex can be recognized by T cells. Human MHC molecules are termed human leukocyte antigens (HLA).
There are two classes of MHC molecules: MHC class I molecules, present on most nucleated cells, present peptides that are generated by proteolytic degradation of endogenous proteins. MHC class II molecules are only found on professional antigen presenting cells (APC), and present peptides of exogenous proteins that are engulfed and processed by APC during endocytosis. Complexes formed between peptide and MHC class I are recognized by CD8-positive cytotoxic T cells, complexes formed between peptide and MHC class II are recognized by CD4 T helper cells.
In order for a peptide to elicit a cellular immune response, it needs to bind to an MHC molecule. This process depends on the allele of the MHC molecule and on the amino acid sequence of the peptide. Usually, MHC class I-binding peptides have a length of 8-10 residues, and their sequences contain two conserved residues (“anchors”) interacting with the corresponding binding groove of the MHC molecule.
In order for the immune system to be able to elicit an effective CTL response against tumor-derived peptides, such peptides not only have to be able to bind to certain MHC class I molecules being expressed by tumor cells, they also have to be recognized by T cells bearing specific T cell receptors (TCR).
The main purpose for developing a tumor vaccine is the identification and characterization of tumor-associated antigens being recognized by CD8+CTL.
The antigens, or their epitopes, that are recognized by the tumor-specific cytotoxic T lymphocytes can be molecules from all protein classes, such as enzymes, receptors, transcription factors, etc. Another important class of tumor-associated antigens are tissue-specific structures such as CT (“cancer testis”) antigens that are expressed in various types of tumors and in healthy testicular tissue. For the proteins to be recognized as tumor-specific antigens by cytotoxic T lymphocytes, and to be therefore used in a therapy, certain conditions must be met: The antigen should mainly be expressed by tumor cells and not or only in smaller amounts by normal cells in contrast to tumors. Furthermore, it is desirable that the respective antigen is present in high concentration not only in one type of tumor but in other tumor types as well. The presence of epitopes in the amino acid sequence of the antigen is also absolutely mandatory since such peptides that are derived from a tumor-associated antigen (“immunogenic peptides”), should lead to a T cell response, either in vitro or in vivo.
Therefore, TAAs are a starting point for the development of a tumor vaccine. The methods for identifying and characterizing the TAAs are based on the use of CTL that have already been induced in the patients, or they are based on the generation of differential transcription profiles between tumors and normal tissues.
However, the identification of genes overexpressed in tumor tissues or human tumor cell lines, or selectively expressed in such tissues or cell lines, does not provide precise information as to the use of the antigens being transcribed from these genes in the immune therapy. This is because only individual epitopes of these antigens are suitable for such an application since only the antigen epitopes—not the entire antigen—elicit a T cell response through MHC presentation. It is therefore important to select only those peptides from overexpressed or selectively expressed proteins that are presented in connection with MHC molecules, so targets for the specific recognition of primary cells or of tumor cell lines established from primary tumor tissue cells, by cytotoxic T lymphocytes could be obtained.
DETAILED DESCRIPTION
Based on this background, it is an objective of the present invention to provide at least one novel amino acid sequence for such a peptide that is capable to bind to a molecule of the human major histocompatibility complex (MHC) class I.
According to the invention this objective is addressed by providing a tumor-associated peptide with an amino acid sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 577 in the attached sequence protocol, whereby the peptide being capable of binding to a molecule of the human major histocompatibility complex (MHC) class I. In this way, the objective forming the basis of the invention is addressed completely.
It is to be understood that the identified tumor peptides may be synthesized to obtain larger quantities or for the use for the below described purposes, or may be expressed in cells.
The inventors were able to isolate and identify the above mentioned peptides from tumor tissue as specific ligands from MHC class I molecules. The term “tumor-associated” peptides herein refers to peptides that are isolated and identified from tumor material. Thus, these peptides that are presented on true (primary) tumors are subjected to antigen processing in a tumor cell.
The specific ligands could be used in cancer therapy, e.g. to induce an immune response against tumor cells expressing the respective antigens from which the peptides are derived.
Such an immune response in form of an induction of CTL may be obtained in vivo. In order to obtain such an immune response the peptide is administered to a patient suffering from a TAA-associated tumor disease, for example in form of a pharmaceutical composition.
On the other hand, a CTL response against a tumor expressing the antigens from which the peptides are derived may also be elicited ex vivo. In order to do so, the CTL precursor cells are incubated together with antigen presenting cells and the peptides. Then, the thus stimulated CTL are cultivated, and these activated CTL are administered to the patient.
Furthermore, it is possible to load APC with the peptides ex vivo, and to administer these loaded APC to the patient expressing in the tumor tissue the antigens from which the peptide is derived. Then, the APC themselves may present the peptide to the CTL in vivo, and thereby activate them.
However, the peptides according to the invention may also be used as diagnostic reagents.
Thus, using the peptides it could be found out if CTL are present in a CTL population or have been induced by a therapy that are specifically directed against a peptide.
The peptides may also be used to test for the increase of precursor T cells with reactivity against the defined peptide.
Furthermore, the peptide may be used as a marker to track the disease course of a tumor expressing the antigen from which the peptide is derived.
The attached Table 1 lists the identified peptides. The table also contains the proteins from which the peptides are derived, and the respective positions of the peptides in the respective proteins which are named or abbreviated by accepted gene symbols according to the “HUGO Gene Nomenclature Committee” (gene.ucl.ac.uk/nomenclature/ or ncbi.nlm.nih.gov/LocusLink/). The English names of the proteins have been maintained to avoid erroneous translations. Furthermore, the Acc numbers are listed that are used in the gene bank of the “National Center for Bio-technology Information” of the National Institute of Health (see ncbi.nlm.nih.gov).
The inventors were able to isolate the peptides (or ligands) from 8 renal cell tumors and 2 glioblastomas from altogether 10 patients, RCC75, RCC98, RCC100, RCC103, RCC112, RCC115, RCC116, RCC130 and NCH359, as well as NCH361, and from a tumor cell line (J-Y).
From the patients' tumors and the cell line J-Y 577 ligands could be identified that were bound to the HLA subtypes A*03, B*07, B*40 (RCC75), A*01, A*03, B*07, B*18 (RCC98), A*02, A*03, B*07, B*18 (RCC100), A*11, A*25, B*15, B*44 (RCC103), A*01, A*31, B*08, B*27 (RCC112), A*02, A*03, B*15, B*18 (RCC115), A*01, A*02, B*27, B*37 (RCC116), A*02, A*24, B*07, B*44 (RCC130), A*03, A*32, B*07, B*35 (NCH359), A*26, B*38 (NCH361) and A*02, B*07 (J-Y).
Some of the ligands are derived from highly expressed so called “housekeeping” genes that are uniformly expressed in most tissues, however, many are characterized by tissue-specific and tumor-specific expression.
Thus, several peptides could be identified that are derived from proteins which are especially overexpressed in tumor tissue. For example, fragments of tenascin-C (GLAPSIRTK, SEQ ID NO. 2) could be identified (Herold-Mende et al., Clinical impact and Functional Aspects of Tenascin-C Expression during Glioma Progression, 2002, Int. J. Cancer, 98: 362-369).
Also, the inventors were able to identify ligands, among others, that are derived from SOX9 (YPHLHNAEL, SEQ ID NO. 7) and RGS5 (LAALPHSCL, SEQ ID NO. 448).
As primary tumor cells are not suited for in vitro culture, the inventors have chosen a human tumor cell line as an example in order to additionally demonstrate that peptides according to the invention identified from this cell line, are suited to activate cytotoxic T lymphocytes in vitro. Particularly, the inventors could show that using a peptide from the established tumor cell line JY as an example, it was possible to generate cytotoxic T lymphocytes (CTL) in vitro that are specific for the selected peptide with the sequence FPSLREAAL (MAGEA1, position 294-302) and SEQ ID NO. 114 and the HLA allele B*0702. Using these CTL, KM22 target cells loaded with the SEQ ID NO. 114 peptide could be selectively killed, whereas KM22 control target cells not loaded with the SEQ ID NO. 114 peptide were not recognized by the cytotoxic T cells. Thus, it could be shown exemplified that human T cells could be activated in vitro using the peptides according to the invention as epitopes. Furthermore, it could be demonstrated that the cytotoxic T lymphocytes lysing the T2 cells loaded with the SEQ ID NO. 114 peptide also express interferon gamma which has been described as a reliable marker for the activation of T cells.
In a preferred embodiment, it is also possible to use peptides for stimulating an immune response that comprise sequence ID NO. 1 to 577, and in which at least one amino acid has been replaced by another amino acid with similar chemical properties.
Referring to the corresponding MHC subtypes, these are, for example, the anchor amino acids that may be replaced by amino acids with similar chemical properties. Thus, for example, in peptides associated with the MHC subtype HLA-A *2, leucine on position 2 may be replaced by isoleucine, valine or methionine and vice versa, and at the C-terminus leucine by valine, isoleucine and alanine, each containing non-polar side chains.
Furthermore it is possible to use peptides with sequence ID No. 1 to 577 comprising at least one additional amino acid N- or/and C-terminally, or in which at least one amino acid is deleted.
Furthermore, peptides with sequence ID No. 1 to 577 may be used in which at least one amino acid is chemically modified.
The varying amino acid(s) is (are) selected in such way that the variation does not affect the immunogenicity of the peptide, i.e. demonstrates a similar binding affinity to the MHC molecule and the capability for T cell stimulation.
According to the invention, the peptide may be used for treatment of tumor diseases and/or adenomatous diseases.
The tumor diseases to be treated comprise, for example, kidney, brain, mammary, pancreas, gastric, testicular and/or skin cancers and tumor diseases of the nerve system. This list of tumor diseases is only exemplary, and is not intended to limit the area of application. The inventors were able to show in independent studies that the peptides according to the invention are suitable for such use. In these studies it was shown that specifically generated CTL that are specific for certain peptides were able to kill tumor cells effectively and selectively.
Basically, for the use of tumor-associated antigens in a tumor vaccine, several application forms are possible. For example, Tighe et al. 1998, Gene vaccination: plasmid DNA is more than just a blueprint, Immunol. Today 19(2):89-97, described that the antigen may be administered either as recombinant protein together with suitable adjuvants or carrier systems, or in form of the cDNA encoding the antigen in plasmid vectors. For this, the antigen needs to be processed and presented by antigen presenting cells (APC) in the patient's body in order for an immune response to be induced.
Melief et al., 1996, Peptide-based cancer vaccines, Curr. Opin. Immunol. 8:651-657, demonstrated another option, namely the use of synthetic peptides as a vaccine.
For this purpose, the peptide may be used in a preferred embodiment together with added adjuvants, or alone.
As an adjuvant, for example, the granulocyte macrophage colony stimulating factor (GMCSF) may be used. Further examples for such adjuvants are aluminum hydroxide, mineral oil emulsions such as, for example, Freund's adjuvant, saponins or silicon compounds.
The use of adjuvants provides the advantage that the immune response induced by the peptide may be enhanced, and/or the peptide may be stabilized.
In another preferred embodiment, the peptide is used bound onto an antigen presenting cell. This measure provides the advantage that the peptides can be presented to the immune system, particularly cytotoxic T lymphocytes (CTL). By this, the CTL are able to recognize the tumor cells and specifically kill them. Suitable as antigen presenting cells for such an application are, for example, dendritic cells, monocytes or B lymphocytes.
For this purpose, the cells are, for example, loaded with peptides ex vivo. On the other hand, it is also possible to transfect the cells with DNA encoding the peptides or with the corresponding RNA to express the peptide on the cells.
The inventors were able to show in independent studies that it is possible to load dendritic cells (DC) with specific peptides, and that these loaded dendritic cells activate peptide-specific CTL. This means that the immune system can be stimulated to raise CTL against the tumors expressing the respective peptides.
The antigen presenting cells carrying the peptide may be used either directly or may be activated prior to their use, for example with the heat shock protein gp96. This heat shock protein induces the expression of MHC class I molecules and co-stimulatory molecules such as B7, and also stimulates the production of cytokines. Together, this supports the induction of immune responses.
In another preferred embodiment, the peptides are used to label leukocytes, especially T lymphocytes.
This application is advantageous if it is intended to use the peptides to find out if CTL are present in a CTL population that are specifically directed against a peptide.
Furthermore, the peptide may be used as a marker to evaluate the progress of a therapy for a tumor disease.
The peptide may be used in other immunizations or therapies for monitoring the therapy as well. Therefore, the peptide may not only be used therapeutically but also diagnostically.
In another embodiment, the peptides are used to generate an antibody.
Polyclonal antibodies may be obtained conventionally by immunizing animals by injection of the peptides and subsequent purification of the immunoglobulin.
Monoclonal antibodies may be generated according to standard protocols, such as, for example, described in Methods Enzymol. (1986), 121, Hybridoma technology and monoclonal antibodies.
In another aspect the invention also relates to a pharmaceutical composition comprising one or more of the peptides.
This composition is used, for example, for parenteral administration, such as subcutaneous, intradermal or intramuscular, or for oral application. For this, the peptides are solved or suspended in a pharmaceutically acceptable, preferably aqueous carrier. Furthermore, the composition may contain excipients such as buffers, binders, diluents, etc.
The peptides may also be given together with immunostimulatory substances such as cytokines. A comprehensive description of excipients that may be used in such compositions is given, for example in A. Kibbe, Handbook of Pharmaceutical Excipients, 3. Ed., 2000, American Pharmaceutical Association and pharmaceutical press.
The preparation may be used for prevention, prophylaxis and/or therapy of tumor diseases and/or adenomatous diseases.
The pharmaceutical preparation containing at least one of the peptides with sequence ID NO. 1 to 577 will be administered to a patient suffering from a tumor disease with which the respective peptide or antigen is associated. Thus, a tumor-specific immune response based on tumor-specific CTL can be elicited.
The amount of the peptide or peptides in the pharmaceutical composition is present in a therapeutically effective amount. The peptides that are present in the composition may also bind to at least two different HLA types.
In a further aspect, the present invention relates to nucleic acid molecules encoding the peptides with sequence ID NO. 1 to 577.
The nucleic acid molecules may be DNA or RNA molecules, and may also be used for immune therapy of cancer diseases. The peptide which is expressed from the nucleic acid molecule induces an immune response against tumor cells expressing the peptide.
According to the invention, the nucleic acid molecules may also be present in a vector.
Furthermore, the invention relates to cells which have been genetically altered using a nucleic acid molecule encoding the peptides so that they produce a peptide with the sequence ID NO. 1 to 577.
For this purpose, the cells are transfected with the DNA encoding the peptides, or with the respective RNA, whereby the peptides are made to be expressed on the cells. As antigen presenting cells for such an approach are suited, for example, dendritic cells, monocytes or B lymphocytes.
It is to be understood that the features that have been mentioned above and that are yet to be discussed below, are suitable not only in the respectively described combination but also alone, without leaving the scope of the present invention.



BRIEF DESCRIPTION OF THE FIGURES
Embodiments of the invention are presented and discussed in the following examples and in the attached figures.
FIG. 1a shows the negative control regarding CTL-specific lysis of KM22 target cells (without peptide);
FIG. 1b shows the CTL-specific lysis of KM22 target cells pulsed with peptide and treated with interferon gamma.
FIG. 2 shows the production of interferon gamma by specific T lymphocytes upon stimulation by KM22 or JY cells loaded with peptide.
FIG. 3 shows the peptide-specific stimulation of human CD8-positive T cells, and
FIG. 4 shows the detection of peptide-specific T cells in blood from renal cell carcinoma patients.
FIG. 5 shows the tetramer analysis of microsphere-driven proliferation of B*0702/IARNLTQQL (SEQ ID NO: 233)-specific CD8+ lymphocytes from peripheral blood. Four (4) out of tested donors (HD155, 159, 161, 177) had significant T cell responses (above the red line) that were directed specifically against the tested peptide antigen with SEQ ID NO. 233, as could be shown by detection of peptide/HLA-B*0702 complex-specific T cell receptors by tetramer staining.



EXAMPLE 1
1.1. Patient Samples
Eight samples were obtained from the Department of Urology at the University of Tubingen, Tubingen, Germany, that were derived from patients with histologically confirmed renal cell carcinoma. The patient termed RCC75 had the following HLA haplotype: A*03, B*07, B*40. The patient termed RCC98 had the following HLA haplotype: A*01, A*03, B*07, B*18, The patient termed RCC100 had the following HLA haplotype: A*02, A*03 B*07, B*18. The patient termed RCC103 had the following HLA haplotype: A*11, A*25, B*15, B*44. The patient termed RCC112 had the following HLA haplotype: A*01, A*31, B*08, B*27. The patient termed RCC115 had following the HLA haplotype: A*02, A*03, B*15, B*18, The patient termed RCC116 had the following HLA haplotype: A*01, A*02, B*27, B*37, and the patient termed RCC130 had following HLA haplotype: A*02, A*24, B*07, B*44.
Two samples were obtained from the Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany, that were derived from patients with histologically confirmed glioblastomas. The patient termed NCH359 had the following HLA haplotype: A*03, A*32, B*07, B*35. The patient termed NCH361 had following HLA haplotype: A*26 and B*38.
1.2. Isolation of MHC Class I-Bound Peptides
Shock frozen tumor samples were processed as previously described in Schirle, M. et al., Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach, 2000, European Journal of Immunology, 30:2216-2225. The peptides were isolated according to standard protocols, using the monoclonal antibody W6/32 which is specific for HLA class I molecules, or using the monoclonal antibody BB7.2 which is specific for HLA-A2. Barnstable, C. J. et al., Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis, 1978, Cell, 14:9-20, and Parham, P. & Brodsky, F. M., Partial purification and some properties of BB7.2. A cytotoxic monoclonal antibody with specificity for HLA-A2 and a variant of HLA-A28, 1981, Hum. Immunol., 3:277-299, have described generation and use of these antibodies.
1.3. Mass Spectroscopy
The peptides were separated by “reversed phase HPLC” (SMART system, μRPC C2/C18 SC 2.1/19, Amersham Pharmacia Biotech), and the obtained fractions were analyzed by nanoESI MS. The approach corresponded to the approach described by Schirle, M. et al., Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach, 2000, European Journal of Immunology, 30:2216-2225.
The peptides obtained from tumor tissue were identified by capillary LC MS, as just described, however with minor modifications: 100 μL of each sample were loaded, desalted and pre-concentrated on a 300 μm*5 mm C18μ guard column (LC Packings). Solvent and sample were added using a syringe pump (PHD 2000, Harvard Apparatur, Inc.) with a sealed 100 μL syringe (1710 RNR, Hamilton) at a speed of 2 μL/min. For separation of the peptides, the pre-concentration column was installed before a 75 μm*250 mm C18 column (LC Packings). Then, a binary gradient with 25-60% B was run for 70 min. during which time the flow rate was reduced from 12 μL/min to approximately 300 nL/min. using a TEE connector (ZTIC, Valco) and a 300 μm*150 mm C18 column.
To ensure that the system was free from peptide residues, a blank was measured respectively. Online-fragmentation was performed as described, and the spectra of the fragments were analyzed manually. Data base searches (NCBInr, EST) were performed using MASCOT (matrixscience.com).
1.4. Identification of the MHC Class I Ligands
In the attached sequence protocol and in the attached table 1 the ligands are listed that were bound to the HLA molecules of patients RCC75, RCC98, RCC100, RCC103, RCC112, RCC115, RCC116, RCC130, NCH359 and NCH361. The peptides associated with HLA-A*02 had an allele-specific peptide motif: on position 2, leucine, valine, isoleucine, alanine, or methionine were found, and at the C-terminus leucine, valine, isoleucine, or alanine. Most of the ligands were derived from so-called “housekeeping” proteins, however, ligands from tumor-associated proteins could be identified as well. For example, fragments from tenascin-C could be identified (GLAPSIRTK, SEQ ID NO. 2; GVLKKVIRH, SEQ ID NO. 20). Herold-Mende et al., Clinical Impact and Functional Aspects of Tenascin-C Expression during Glioma Progression, 2002, Int. J. Cancer, 9S: 362-369, show that in general the strength of the expression of the extracellular matrix protein tenascin-C correlates with the severity of the disease and the immigration of tumor cells in healthy tissue.
1.5. Detection of Peptide-Specific T Cells in the Normal CD8+ T Cell Repertoire
For detection of peptide-specific T cells, for example specific for the peptide with the sequence FPSLREAAL (SEQ ID NO. 114), mononuclear cells from peripheral blood of healthy subjects were stained with the corresponding HLA-A* subtype tetramers constituted with the respective peptides: To generate the tetramers, recombinant HLA-B* subtype molecules were constituted in vitro with the peptides, purified by gel filtration, biotinylated, and mixed with streptavidin for linking the monomers, as described by Walter S. et al., 2003, Cutting Edge: Predetermined Avidity of Human CDS T Cells Expanded on Calibrated MHC/Anti-CD2S-Coated Microspheres, J. Immunol. 171: 4974-4978.
Basically, the results of the double staining are measured by FACS analysis, and the specific binding of the peptide tetramers is detected (Walter S. et al., 2003, Cutting Edge: Predetermined Avidity of Human CDS T Cells Expanded on Calibrated MHC/Anti-CD2S-Coated Microspheres, J. Immunol. 171: 4974-4978).
EXAMPLE 2
To analyze the presentation of the selected peptides by tumor cells and the recognition of the peptides by CTL, CTL were induced in vitro that are specific for the chosen peptides. For this purpose, KM22 and JY target cell lines were used.
2.1. Recovery of the Specific T Lymphocytes
Specific T lymphocytes were isolated from the blood of healthy subjects as described in 1.5 and concentrated by FACS sorting.
2.2. Peptide Synthesis
The peptides chosen as an example were synthesized using F-moc (9-f luorenylmethyloxycarbonyl) protection groups on a peptide synthesizer (432A, Applied Biosystems, Weiterstadt, Germany) and analyzed by “reversed phase” HPLC and mass spectroscopy. Thereby, sufficient amounts of the identified peptides could be produced.
2.3. Induction of an Antigen-Specific CT1 Response Using Restricted Synthetic Peptides
For CTL induction, the T lymphocytes obtained in step 2.1 (5×106 T lymphocytes per well) were co-incubated by in vitro restimulation in 24-well plates with 1×106 irradiated target cells per well in 1.5 mL T cell medium [consisting of RPMI 1640, 25 mM HEPES (Life Technologies/Invitrogen, Karlsruhe, Germany)] with 10% heat-inactivated human AB serum (CC Pro, Neustadt/Weinstraβe, Germany), 2 mM L-glutamine, 50 U/mL penicillin, 50 mg/mL streptomycin, and 20 μg/mL gentamicine (all from Bio Whittaker/Cambrex, Verviers, Belgium). Additionally, 5 ng/mL human IL-12 p70 (R&D Systems) were added. After approximately 4 days co-incubation at 37° C., fresh medium was added with 20 U/mL human IL-2 (R&D Systems), and the cells were incubated for another 3 to 4 days. This stimulation cycle was repeated twice.
2.4. CTL Assay
For the CTL assays, KM22 and JY tumor cell lines were used as target cells. Peptide-pulsed cells were pulsed with 50 μg/mL peptide for 2 hours. All target cells were labeled in RP10 medium (RPMI 1640, supplemented with 10% heat-inactivated fetal calf serum and antibiotics) for 1 hour at 37° C. with [51Cr] sodium chromate (51Cr). Then, 104 cells/well were added to a 96-well round bottom plate. Various numbers of CTL were added to obtain an end volume of 200 μL, with subsequent incubation for 4 hrs at 37° C. Then, supernatants (500 μL/well) were harvested and counted in a beta-plate counter. Specific lysis was calculated in percent as follows: 100×(experimental release−spontaneous release/maximum release−spontaneous release). Each, spontaneous and maximum release were determined in presence of either medium or 2% Triton X-100.
2.5. Results of the CTL Induction
a) CTL Cytotoxic Activity Compared to Peptide-Pulsed Target Cells
In 51Cr release assays (see 2.4.) the cytotoxic activity of induced CTL (see 2.3.) was tested and compared to KM22 and JY cells. Cell lines KM22 and JY are HLA-B*07 positive.
The results of these release assays are shown in FIGS. 1a and 1b. In FIGS. 1a and 1b, the abbreviation “IFN” stands for interferon gamma, “E:T” stands for the ratio of effector to target cells, “Tet+” stands for T lymphocytes binding to HLA-B*0702/FPSLREAAL (SEQ ID NO: 114) tetramers, and “Tet-” stands for T lymphocytes not binding to HLA-B*0702/FPSLREAAL (SEQ ID NO: 114) tetramers.
The results show that an antigen-specific kill of the cells can be obtained with CTL cell lines that have been obtained after restimulation for 2 weeks.
In FIG. 1a is shown that KM22 target cells treated with interferon gamma and positive for HLA allele B*0702 without peptide were not recognized by specific cytotoxic T lymphocytes.
FIG. 1b shows that KM22 target cells, treated with interferon gamma, positive for HLA allele B*0702 presenting the peptide with the sequence FPSLREAAL (SEQ ID NO: 114) from the tumor antigen MAGE-1 are recognized and lysed by specific cytotoxic T lymphocytes. Thus, only those cells were killed by an increasing number of CTL that presented the respective selected peptides; the control cells loaded with irrelevant peptides were not killed. By this, the specificity of the cytolytic activity could be demonstrated.
b) Production of Interferon Gamma by Peptide-Stimulated T Lymphocytes
In another experiment it was shown that the cytotoxic T lymphocytes lysing the T2 cells loaded with peptide FPSLREAAL (SEQ-ID NO. 114) also expressed interferon gamma which has been described as a reliable marker for activation of T cells.
In FIG. 2, the results of the measurements are shown, with KM22 and JY cells being tested. The same abbreviations as in FIG. 1 were used, with “CD8+” describing T lymphocytes expressing the receptor molecule CD8 on the cell surface.
To detect IFN gamma, 1×105 effector cells and stimulator cells that have been pulsed with peptide were grown in T cell medium on 96-well plates (T cell medium: RPMI 1640 with 25 mM HEPES (Gibco/Invitrogen, Karlsruhe, Germany; supplemented with 10% heat-inactivated human AB serum (CC pro, Neustadt/W., Germany; 2 mM L-glutamine, 50 U/mL penicillin, 50 μg/mL streptomycin and 20 μg/mL gentamycine (all from BioWhittaker). The loading with peptides was conducted in X-Vivo 15 medium with the respective peptides for approx. 2 hrs at 37° C.
After 1 to 2 hrs GolgiStop (Becton Dickinson) was added and incubated for another 4 to 5 hrs. Then, the cells were permeabilized and stained by using the Cytofix/Cytoperm Plus kit as well as anti-CD4-FITC, anti-IFN-•-PE and anti-CD8-PerCP according to the manufacturer's recommendations (Becton Dickinson). The cytometric analysis was performed using a FACSCalibur cytometer.
As can be seen from FIG. 2, T lymphocytes binding to HLA-B*0702/FPSLREAAL (SEQ ID NO: 114) tetramer (=specific T lymphocytes, “Tet+”) produce interferon gamma, when they are stimulated with KM22 or JY cells, each pretreated with various amounts of interferon gamma and loaded with peptide with SEQ ID NO. 114 (see FIG. 2, “KM22+FPSLREAAL (SEQ ID NO: 114)” and “JY+FPSLREAAL (SEQ ID NO: 114)”, each pretreated with 5 or 25 μM INF). In contrast, unspecific T lymphocytes (which do not bind to the HLA-B*0702/FPSLREAAL (SEQ ID NO: 114) tetramer) do not produce any interferon gamma (=“Tet-”).
Furthermore, FIG. 2 shows that neither the specific (=“Tet+”) nor the unspecific (“Tet-”) T lymphocytes produced interferon gamma if they were stimulated with an unspecific control peptide (in FIG. 2 as an example: APRTVALTA, SEQ ID NO. 585) (see FIG. 2 for “Tet+” and “Tet-”, respectively: “KM22+APRTVALTA (SEQ ID NO: 585)” and “JY+APRTVALTA (SEQ ID NO: 585)”, each pretreated with 25 μM INF).
c) Peptide-Specific Stimulation of CD8-Positive T Cells
For further determination of the peptide-specific stimulation of CD8-positive T cells the peptide with sequence LAALPHSCL (SEQ ID NO. 448) from protein RGS-5 and the control peptide with sequence ELAGIGILTV (SEQ ID NO. 578) from melanoma antigen MELAN-A (position 26-35, modified by an amino acid exchange of the alanine at position 27 by leucine) were synthesized using standard Fmoc chemistry, with the control peptide also binding to the HLA allele A*02. Biotinylated recombinant A*02 molecules and fluorescent MHC tetramers were generated as described by Altman et al. (“Phenotypic analysis of antigen-specific T lymphocytes”, Science 274:94, 1996). To generate artificial antigen presenting cells (“APCs”), streptavidin-coated polystyrene particles (5.6 μm diameter) with a binding capacity of 0.064 μg biotin-FITC/mg microspheres (Bangs Laboratories, Fishers, Ill., USA) were resuspended with 2×106 particles/mL in a buffer containing the biotinylated MHC and the antibodies, and incubated for 30 min. at room temperature.
For the antigen-specific in vitro stimulation of the human CD8 T cells, PBMC from fresh buffy coat were isolated by standard gradient separation. Untreated CD8 T cells were concentrated by negative depletion using MACS (Miltenyi Biotec, Bergisch Gladbach, Germany). The in vitro stimulations were performed on 24-well plates with 5×106 responder cells and 1×106 beads or 1×106 irradiated APCs per well in 1.5 mL T cell medium (compare supra). 5 ng/mL human IL-12 p70 (R&D Systems, USA) were added together with microspheres. After 3 to 4 days co-incubation at 37° C., fresh medium and 20 U/mL human IL-2 (R&D Systems, USA) were added, and the cells were incubated for another 3 to 4 days. This stimulation cycle was repeated twice.
For the cell surface and intracellular cytometric analysis, tetramer analyses with fluorescent MHC tetramers plus anti-CD8 antibodies (hybridoma UKT8) were conducted on a four-color FACSCalibur (Becton Dickinson).
The results of these analyses are shown in FIG. 3. It can be seen that the RGS-5 peptide with SEQ ID NO. 448 specifically stimulates human CD8-positive T cells. In FIG. 3, in the left column, the analysis of PBMC T cells is shown that have been stimulated twice with a control peptide with the sequence ELAGIGILTV from melan-A (SEQ ID NO. 578), as described above. The right column shows the analyses of T cells that have been stimulated with the RGS-5 peptide with the sequence LAALPHSCL (SEQ ID NO. 448).
In the top left of FIG. 3 is shown that CD8-positive (x-axis) T cells stimulated with melan-A peptide/MHC-A*02 tetramer complexes do not bind to MHC-A*02 tetramers complexed with the peptide with the sequence LAALPHSCL (SEQ ID NO. 448) (y-axis).
In the top right of FIG. 3 is shown that CD8-positive T cells, stimulated with RGS-5 peptide with the sequence LAALPHSCL (SEQ ID NO. 448)/MHC-A*02 tetramer complexes, bind to MHC-A*02 tetramers complexed with the peptide with the sequence LAALPHSCL (SEQ ID NO. 448) (y-axis). The double-stained (double-positive) cells are shown in the upper right quadrant.
In FIG. 3, left middle, is shown that CD8-positive T cells (x-axis) stimulated with melan-1 peptide/MHC-A*02 tetramer complexes, bind to MHC-A*02 tetramers complexed with the peptide with the sequence ELAGIGILTV (SEQ ID NO. 579) from melan-A (y-axis). The double stained (double positive) cells are shown in the upper right quadrant. In the right middle is shown that CD8-positive T cells, stimulated with complexes from RGS-5 peptide with the sequence LAALPHSCL (SEQ ID NO. 448) and MHC-A*02 tetramers, not bind to MHC-A*02 tetramers complexed with the peptide with the sequence ELAGIGILTV (SEQ ID NO. 579) from melan-A (y-axis).
In the bottom row of FIG. 3, on the left hand side, the proportional numbers of the melan-A/MHC-A*02-specific T cells are shown by double staining with the two applied MHC tetramer-peptide complexes (melan-A/MHC-A*02 and RGS-5/MHC-A*02). After prior stimulation with melan-A peptide/MHC-A*02 tetramer complexes bound on artificial antigen presenting cells, 19.3% of the stimulated cells bind specifically to the MHC tetramer complex of melan-A peptide and HLA-A*02. On the bottom right hand side, the proportional numbers of the RGS-5/MHC-A*02-specific T cells are shown by double staining with the two applied MHC tetramer complexes (melan-A/MHC-A*02 and RGS-5/MHC-A*02). After prior stimulation with RGS-5 peptide/MHC-A*02 tetramer complexes bound on artificial antigen presenting cells, 8.0% of the stimulated cells bind specifically to the MHC tetramer complex of RGS-5 peptide with the sequence LAALPHSCL (SEQ ID NO. 448) and HLA-A*02.
d) Detection of Peptide-Specific T Cells in Blood from Renal Cell Carcinoma Patients
In further experiments, peptide-specific T cells from blood from renal cell carcinoma patients previously immunized with peptide-loaded autologous dendritic cells could be detected.
For this detection, a quantitative real-time polymerase chain reaction (RT-PCR) was performed. This RT-PCR was conducted as described by Kammula et al. (Kammula et al., Journal of Immunology 163:6867, 2000). For this, PBMCs were thawed in T cell medium, plated out with 1×106 cells in 500 μL medium and incubated over night with 5% CO2 at 37° C. Then, the synthetic peptides were added with 5 μg/mL for 3 hours, and then an RNA extraction with Trizole (Invitrogen, Karlsruhe, Germany) was performed. The cDNA was transcribed using random hexamer primers (Amersham Biosciences, Freiburg, Germany) and M-MLV reverse transcriptase (Promega GmbH, Mannheim, Germany).
The quantitative RT-PCR was performed on an “ABIPrism 7000 Sequence Detection System” (Applied Biosystems, Darmstadt, Germany) in duplicate in respect to IFN gamma mRNA and CD8 mRNA, using the Taqman PCR master mix (Applied Biosystems), specific primers and fluorescent probes.
The results represent the copy number of IFN gamma mRNA, with each sample being normalized regarding the CD8 mRNA copy number (used as reference gene product) (stimulation index). The gene expression in presence of the tested peptides is relative to the gene expression obtained in presence of the controls (HLA-A*02 epitope derived from HIV1 pol with the sequence ILKEPVHGV, SEQ ID NO. 579) (copy number of the control was set to 1).
In FIG. 4 the results of these studies are shown. The diagram in FIG. 4 shows the ex vivo T cell activation after immunization of the patient RCC98 at the University Hospital in Tübingen with nine HLA-binding peptides. The first two out of 11 column blocks show the negative and positive controls of the T cell experiment. The error bars represent the standard deviation. As mentioned above, the HIV peptide with the sequence ILKEPVHGV (from the viral antigen HIV1 pol, position 896-904; SEQ ID NO. 579) was used as negative control. The negative control did not lead to a T cell response if the patient was seronegative for HIV. As a positive control, a mixture of peptides from influenza matrix 58-66 (GILGFVFTL; SEQ ID NO. 580), HCMVA pp 65 495-503 (NLVPMVATV; SEQ ID NO. 581), EBNA6-EBV 284293 (LLDFVRFMGV; SEQ ID NO. 582), IE63-EBV 259-267 (GLCTLV AML; SEQ ID NO. 583), and LMP2-EBV 294-302 (CLGGLLTMV; SEQ ID NO. 584) was used, with which as very strong T cell response could be expected (“posmix”; Maximum: stimulation index 43.6). All control peptides for PBMC stimulation were used in a concentration of 5 μg/mL. The background was defined as standard deviation of the negative control (stimulation index 1.35, shown as horizontal dashed line).
In FIG. 4, the next nine column blocks of the diagram show the T cell activations measured against nine immunized peptides. These nine peptides were administered together subcutaneously, altogether seven times in increments of 14 days, loaded onto autologous dendritic cells. Therefore, each column block consists of eight columns (before the 1st immunization, after the 1st immunization, after the 2nd immunization, etc.). Therefore, each column block shows the progression of the T cell responses in the course of the immunizations.
Starting after the 3rd immunization already, strong T cell responses were obtained for GLASFKSFLK (RGS-5 74-83, SEQ ID NO. 153) and SLLTSSKGQLQK (ADFP 369-380, SEQ ID NO. 289), whereby for the last peptide the T cell responses increased after the 4th immunization. Such fluctuations of the T cell response during the course of an immunization therapy are known from other patients as well.
For IARNLTQQL (ADFP 313-321; SEQ ID NO. 233), GPALGRSFL (TNFSF7 78-86, SEQ ID NO. 577) the T cell responses were clearly in the background, and were weaker for a known pan-HLA DR-binding (PADRE) peptide. For these three peptides, an increase of the T cell response was also observed during the course of the immunization therapy (dotted lines). This confirmed that these three latter peptides have elicited a positive T cell response.
The patient was immunized as part of a registered clinical study at the University Hospital in Tubingen, Germany. The clinical study was applied and approved in written form by the Ethical Committee of the University of Tubingen, Germany. The study was conducted according to the rules and regulations of the German Medicines Act (Arzneimittelgesetz) and the good clinical practice (GCP).
In summary, the inventors were thereby able to show that the identified peptides represent promising substances as part of an immunotherapy for a variety of (tumor) diseases.
EXAMPLE 3
Tetramer analysis of the microsphere-driven proliferation of B*0702/IARNLTQQL (SEQ ID NO. 233)-specific CD8+ lymphocytes from peripheral blood (see FIG. 5).
1×106 CD8+ enriched PBMCs per well from six healthy HLA-A*0201+ donors HD155, HD159, HD161, HD167, 00168 and 00177, were stimulated weekly with microspheres coupled to anti-CD28 plus irrelevant antigen (“irrelevant stimulation”), tumor antigen B*0702/IARNLTQQL (SEQ ID NO. 233) with high density (“HD”) or tumor antigen B*0702/IARNLTQQL (SEQ ID NO. 233) with low density (“LD”) as previously shown [Walter, S, et al. Cutting Edge: Predetermined avidity of human CD8 T cells expanded on calibrated MHC/anti-CD28-coated microspheres. J. Immunol. 171 (1 0):4974-8, 2003] with minor modifications. After three stimulations in vitro, individual wells were stained with antibody CD8 plus tetramer B*0702/IARNLTQQL (SEQ ID NO. 233). Each dot represents the percentage of tetramer+ among CD8+ lymphocytes from one well.
Based on the distribution of observed responses after irrelevant stimulation in individual donors, a significant threshold was calculated, and shown by a horizontal red line using the following formula:

Threshold=upper limit of 95% confidence interval for the mean+3×upper limit of 95% confidence interval for the standard deviation

The numbers in the diagrams show the number of significantly positive wells among total wells for the indicated condition.











TABLE 1






Sequence
Position/Gene symbol
Acc. No.
SEQ ID NO.
















Sequences of NCH359













1.
VPDSSGPERIL
78-88
NP_002131.2
SEQ ID NO. 1





HNRPK


 


2.
GLAPSIRIK
1510-1518
NP_002151.1
SEQ ID NO. 2




TNC


 


3.
RLFEHPLYR
149-157
NP_064608.1
SEQ ID NO. 3




FAM20C


 


4.
TPSEPHPVL
381-389
NP_057342.1
SEQ ID NO. 4




HGRG8


 


5.
QIFVKTLTGK
2-11
AAH01392.1
SEQ ID NO. 5




RPBS27A


 


6.
SLMHSFILK
44-52
NP_054902.1
SEQ ID NO. 6




DNCL2A


 


7.
YPHLHNAEL
127-135
NP_000337.1
SEQ ID NO. 7




SOX9


 


8.
RLFVGSIPK
244-252
NP_006363
SEQ ID NO. 8




SYNCRIP


 


9.
RVFPDKGYSF
233-242
NP_071320.1
SEQ ID NO. 9




TIA1


 


10.
SLYKKLEIK
554-562
NP_003039.2
SEQ ID NO. 10




SLC9A2


 


11.
HPVSDHEAUL
216-225
NP_002108
SEQ ID NO. 11




HLA-C


 


12.
LPTRVDFSL
46-54
BAC87610
SEQ ID NO. 12




Symbol does not




exist;




Gene type: unnamed




protein product


 


13.
KSFGSAQEFAW
386-396
NP_004757
SEQ ID NO. 13




COPB2


 


14.
SPSTSRTPLL
1026-1035
NP_005219.2
SEQ ID NO. 14




EGFR


 


15.
STFDSPAHW
1149-1157
NP_005219.2
SEQ ID NO. 15




EGFR


 


16.
APEEHPVLL
97-105
NP_001092.1
SEQ ID NO. 16




ACTB


 


17.
RQITQVYGF
117-125
NP_002712.1
SEQ ID NO. 17




PPP6C


 


18.
KVSDYILQH
1046-1054
NP_054729.3
SEQ ID NO. 18




ASTN2


 


19.
KLLPSVVLK
210
NP_001936.1
SEQ ID NO. 19




DTR


 


20.
GVLKKVIRH
23-31
NP_002151.1
SEQ ID NO. 20




TNC


 


21.
KLFDHAVSKF
40-49
NP_004449.1
SEQ ID NO. 21




ACSL4


 


22.
ITVLTKPLPV
112-121
NP_002839.1
SEQ ID NO. 22




PTPRO


 


23.
HPVHBPIKL
130-138
NP_057250.1
SEQ ID NO. 23




PIAS1


 


24.
IPRAALLPLL
3-12
NP_002766.1
SEQ ID NO. 24




PRSS11


 


25.
ATNRITVTW
254-262
NP_056981.2
SEQ ID NO. 25




PIASY


 


26.
KIADRFLLY
29-37
NP_006760.1
SEQ ID NO. 26




LMO4


 








Sequences of NCH361













27.
DHDPVDKIVL
150-159
NP_002128.1
SEQ ID NO. 27





HNRPA2P1


 


28.
DHHQEVIGF
165-173
NP_055427.2
SEQ ID NO. 28




C9ORF10


 


29.
IHDLDNISF
188-196
NP_002785.1
SEQ ID NO. 29




PSMB2


 


30.
DHINDIIKI
834-842
NP_003861.1
SEQ ID NO. 30




IQGAP1


 


31.
DHMRFISEL
355-363
NP_055423.1
SEQ ID NO. 31




CYFIP1


 


32.
THSLPVVVI
456-464
NP_003141.2
SEQ ID NO. 32




STAT3


 


33.
MPVGPDAILRY
929-939
NP_004630.2
SEQ ID NO. 33




BAT3


 


34.
RLDDAIHVL
406-414
NP_003196.1
SEQ ID NO. 34




TCF12


 


35.
QHEGTVNIF
1953-1961
NP_002842.1
SEQ ID NO. 35




PTPRZ1


 


36.
ETVNIWTHF
48-56
NP_940798
SEQ ID NO. 36




PAQR6


 


37.
VHILDTETF
195-203
NP_055130.1
SEQ ID NO. 37




KLHDC2


 


38.
QTPDFTPTKY
607-616
NP_055850.1
SEQ ID NO. 38




ZHX3


 


39.
RHVEVFELL
133-141
NP_003820.1
SEQ ID NO. 39




MPDZ


 


40.
TTIDIGVKY
136-144
NP_001830.1
SEQ ID NO. 40




CNN3


 


41.
DLIEHFSQF
113-121
NP_006796.1
SEQ ID NO. 41




HNRPA0


 


42.
ETVWRLEEF
65-73
NP_061984
SEQ ID NO. 42




HLA-DRA


 


43.
DVLESVNLL
176-184
NP_004059.2
SEQ ID NO. 43




AP2M1


 


44.
IHDDFVTTF
466-474
NP_001120.2
SEQ ID NO. 44




AEBP1


 


45.
IHIBINNII
57-65
NP_055117.1
SEQ ID NO. 45




Sec61G


 


46.
IHLIDPNTL
281-289
NP_057022.2
SEQ ID NO. 46




CGI-07


 


47.
IHVIGGNDV
1016-1024
XP_291055.1
SEQ ID NO. 47




KIAA1268


 


48.
KAFQKIVVL
291-299
NP_055485.2
SEQ ID NO. 48




BZW1


 


49.
YQDLLNVKL
349-357
NP_002046.1
SEQ ID NO. 49




GFAP


 


50.
GHYEVAELL
728-736
NP_003738.1
SEQ ID NO. 50




TNKS


 


51.
LVVYPWTQRF
33-42
NP_000509.1
SEQ ID NO. 51




HBB


 


52.
MHLRQYELL
386-393
NP_000507.1
SEQ ID NO. 52




GNAS


 


53.
EAIEQILKY
149-157
NP_060600.1
SEQ ID NO. 53




FLJ10539


 


54.
DVAEGDLIEHF
108-118
NP_006796.1
SEQ ID NO. 54




HNRPA0


 


55.
DVLQKIKY
191-198
NP_060199.2
SEQ ID NO. 55




EPS8L1


 


56.
DSFPMEIRQY
24-33
NP_009330.1
SEQ ID NO. 56




STAT1


 


57.
DVISNIETF
281-289
NP_000337.1
SEQ ID NO. 57




SOX9


 


58.
DVIRLIMQY
9-17
NP_060695.1
SEQ ID NO. 58




SMU-1


 


59.
DVIERVIQY
792-800
NP_056199.1
SEQ ID NO. 59




IDN3


 


60.
DVIAQGIGKL
53-62
NP_000995.1
SEQ ID NO. 60




RPLP2


 


61.
DVFNEKGWNY
94-103
NP_005737.1
SEQ ID NO. 61




PBEF1


 


62.
THLDSVTKI
254-262
NP_077308.1
SEQ ID NO. 62




C6.1A


 


63.
DVAGIIADY
294-302
XP_048675.4
SEQ ID NO. 63




KIAA1238


 


64.
TAAPFPFHL
536-544
NP_005985.2
SEQ ID NO. 64




TBX2


 


65.
DTLDKVFTY
86-94
NP_004448.2
SEQ ID NO. 65




ACSL3


 


66.
DTISPTLGF
42-50
NP_001658.1
SEQ ID NO. 66




ARL2


 


67.
DTGILDSIGRF
35-45
NP_002376.1
SEQ ID NO. 67




MBP


 


68.
VVYPWTQRF
34-42
NP_000509.1
SEQ ID NO. 68




HBB


 


69.
EVVAGIKEYF
128-137
NP_006783.2
SEQ ID NO. 69




MORF4


 


70.
SSVPGVRLL
72-80
NP_003371.1
SEQ ID NO. 70




VIM


 


71.
SVVDAIGISRF
364-374
BAC86883.1
SEQ ID NO. 71




FLJ45273


 


72.
EVIPPMKEF
115-123
NP_002484.1
SEQ ID NO. 72




NDUFB6


 


73.
EVIPPYYSY
152-160
NP_057698.2
SEQ ID NO. 73




TTRAP


 


74.
EVNGLISMY
284-292
NP_004238.2
SEQ ID NO. 74




U5-116KD


 


75.
EVIDLMIKEY
57-66
NP_060758.1
SEQ ID NO. 75




PHF10


 


76.
EVVAGIKEY
128-136
NP_006783.2
SEQ ID NO. 76




MORF4


 


77.
EVFPLAMNY
76-84
NP_444284.1
SEQ ID NO. 77




CCND1


 


78.
EVVERVLTF
28-36
NP_036302.1
SEQ ID NO. 78




FBXO22


 


79.
SHSPFGLDSF
1251-1260
NP_057688.2
SEQ ID NO. 79




JMJD1B


 


80.
FGVDRAILY
457-465
NP_002201.1
SEQ ID NO. 80




ITGAV


 


81.
SHSDYLLTI
76-84
NP_003868.1
SEQ ID NO. 81




SOCS2


 


82.
SHLDYDITL
511-519
XP_087353.5
SEQ ID NO. 82




KIAA0794


 


83.
SHFVSDVVI
63-71
NP_006089.1
SEQ ID NO. 83




GNB2L1


 


84.
EVTELLARY
155-163
NP_002686.2
SEQ ID NO. 84




POLR2E


 


85.
ETADTLMGLRY
425-435
NP_002047.1
SEQ ID NO. 85




GFPT1


 


86.
EHAHLIVVL
662-670
NP_062570.1
SEQ ID NO. 86




ABCB9


 


87.
EHSLVIDTL
53-61
NP_036526.2
SEQ ID NO. 87




PFDN2


 


88.
EIAEAYLGY
129-137
NP_005336.2
SEQ ID NO. 88




HSPA1A


 


89.
EIYGGSDSRF
42-51
NP_036565.1
SEQ ID NO. 89




SF3B1


 


90.
ELIAKIPNF
73-81
NP_003002.1
SEQ ID NO. 90




SET


 


91.
EVIKNFIQY
50-58
NP_057175.1
SEQ ID NO. 91




EIF3S6IP


 


92.
ETADTLLALRY
426-436
NP_005101.1
SEQ ID NO. 92




GFPT2


 


93.
EVVSEPFRSF
581-590
NP_002799.3
SEQ ID NO. 93




PSMD2


 


94.
ETFDAGLQAF
2019-2028
NP_003118.1
SEQ ID NO. 94




SPTAN1


 


95.
SHSQLMQLI
164-172
NP_008933.2
SEQ ID NO. 95




ADRM1


 


96.
ETVRELTEF
255-263
NP_006229.1
SEQ ID NO. 96




PPARD


 


97.
EVAATEIKM
10-18
NP_005959.2
SEQ ID NO. 97




HNRPM


 


98.
EVAAVLLHF
214-222
NP_006535.1
SEQ ID NO. 98




SEC10L1


 


99.
EVFDKTYQF
132-140
NP_149103.1
SEQ ID NO. 99




C6orf153


 


100.
ELVKRILNF
174-182
NP_003463.1
SEQ ID NO. 100




DEK


 


101.
AHDDGRWSL
95-103
NP_003079.1
SEQ ID NO. 101




FSCN1


 


102.
SVVSVISRF
4-12
NP_001335.1
SEQ ID NO. 102




DAD1


 


103.
SVVELINHY
132-140
NP_003620.2
SEQ ID NO. 103




PIK3R3


 


104.
SVVDLINHY
397-405
NP_005018.1
SEQ ID NO. 104




PIK3R2


 


105.
AHVDLIEKL
51-59
NP_066951.1
SEQ ID NO. 105




POLR2L


 


106.
FHNELLTQL
97-105
NP_006331.1
SEQ ID NO. 106




BAIAP2


 


107.
SVIEAVAHF
812-820
NP_056070.1
SEQ ID NO. 107




C6orf133


 


108.
GHFEKPLFL
149-157
NP_006693.2
SEQ ID NO. 108




NTE


 


109.
GHDASQITL
273-281
NP_057481.2
SEQ ID NO. 109




TH1L


 


110.
SAVDFIRTL
293-301
NP_004751.1
SEQ ID NO. 110




STK17A


 


111.
ISTPVIRTF
989-997
NP_055427.2
SEQ ID NO. 111




C9orf10


 


112.
GVIEKLLTSY
28-37
AAH32446
SEQ ID NO. 112




D1S155E


 


113.
SHDLTLVNL
395-403
NP_085139.1
SEQ ID NO. 113




KIAA1706


 








Sequence of JY













114.
FPSLREAAL
294-302
NP_004979.2
SEQ ID NO. 114





MAGEA1


 







Sequences of RCC075












115.
SIFKQPVTK
250-258
NP_003918.1
SEQ ID NO. 115





MBD2


 


116.
KPNANRIAL
139-147
NP_002297.1
SEQ ID NO. 116




LGALS3


 


117.
KLYEMILKR
174-182
NP_00S728.2
SEQ ID NO. 117




ARL7


 


118.
SLFSRLFGK
7-15
NP_0016S1.1
SEQ ID NO. 118




ARF4


 


119.
KLFDKLLEY
309-317
NP_006S86.1
SEQ ID NO. 119




API5


 


120.
SLFPNSPKWTSK
96-107
NP_002414.1
SEQ ID NO. 120




MMP7


 


121.
LESLDQLEL
29-37
NP_004273.1
SEQ ID NO. 121




BAG2


 


122.
VVNKVPLTGK
101-110
NP_689474.1
SEQ ID NO. 122




MGC17943


 


123.
SVYDSVLQK
4470-4478
NP_149062.1
SEQ ID NO. 123




SYNE1


 


124.
SVYVLVRQK
39-47
NP_11S604.1
SEQ ID NO. 124




MLSTD2


 


125.
ILENIQRNK
557-565
NP_000391.1
SEQ ID NO. 125




ERCC2


 


126.
GSYNKVFLAK
146-155
NP_002803.1
SEQ ID NO. 126




PSMD8


 


127.
TESGLNVTL
6-14
NP_006187.1
SEQ ID NO. 127




PCBP1


 


128.
TEHGVEVVL
612-620
NP_00S480.1
SEQ ID NO. 128




SH2D3C


 


129.
TEARFGAQL
327-335
NP_002267.2
SEQ ID NO. 129




KRT19


 


130.
TLADILLYY
114-122
NP_004271.1
SEQ ID NO. 130




EEF1E1


 


131.
LVFPSEIVGK
133-142
NP_001002.1
SEQ ID NO. 131




RPS7


 


132.
VLFGKALNPK
709-718
NP_003777.2
SEQ ID NO. 132




ABCC3


 


133.
RPELVRPAL
91-99
NP_003730.4
SEQ ID NO. 133




AKR1C3


 


134.
VPNQKRLTLL
576-585
NP_004449.1
SEQ ID NO. 134




ACSL4


 


135.
QLYWSHPRK
5-13
NP_001023.1
SEQ ID NO. 135




RPS29


 


136.
SVYVYKVLK
39-47
NP_059141.1
SEQ ID NO. 136




H2BFS


 


137.
REKLQEEML
186-194
NP_003371.1
SEQ ID NO. 137




VIM


 


138.
RVFSGLVSTGLK
415-426
NP_001952.1
SEQ ID NO. 138




EEF2


 


139.
KPRDVSSVEL
1939-1948
NP_003119.1
SEQ ID NO. 139




SPTBN1


 


140.
NEFPEPIKL
184-192
NP_004628.4
SEQ ID NO. 140




RAB7


 


141.
KTYGEIFEK
106-114
NP_004540.1
SEQ ID NO. 141




NDUFC2


 


142.
RILFFNTPK
196-204
NP_002803.1
SEQ ID NO. 142




PSMD8


 


143.
RVFPWFSVK
1764-1772
NP_005924.1
SEQ ID NO. 143




MLL


 


144.
SEVQDRVML
54-62
NP_057145.1
SEQ ID NO. 144




CGI-127


 


145.
SLWDRLIFH
410-418
NP_001986.2
SEQ ID NO. 145




ACSL1


 


146.
KVYNIQIRY
468-476
NP_005556.1
SEQ ID NO. 146




LCP2


 


147.
RLLEMILNK
171-179
NP_001345.1
SEQ ID NO. 147




AKR1C2


 


148.
SEDKKNIIL
41-49
NP_005498.1
SEQ ID NO. 148




CFL1


 


149.
YEELVRMVL
106-114
NP_524147.1
SEQ ID NO. 149




MYL6


 


150.
GEITGEVHM
1758-1766
NP_001448.1
SEQ ID NO. 150




FLNB


 


151.
IVAGSLITK
183-191
AAH11788
SEQ ID NO. 151




FNBP3


 


152.
APRIITGPAPVL
225-236
NP_006766.1
SEQ ID NO. 152




QKI


 


153.
GLASFKSFLK
74-83
NP_003608.1
SEQ ID NO. 153




RGS5


 


154.
FPNSPKWTSK
98-107
NP_002414.1
SEQ ID NO. 154




MMB7


 


155.
FVIETARQL
49-57
NP_078772.1
SEQ ID NO. 155




Cl4orf4


 


156.
IEVDGKQVEL
46-55
NP_001655.1
SEQ ID NO. 156




RHOA


 


157.
GELTGEVRM
1776-1786
NP_001449.1
SEQ ID NO. 157




FLNC


 


158.
GESDDSILRL
63-72
NP_001015.1
SEQ ID NO. 158




RPS21


 


159.
GEGDFLAEGGGV
23-34
NP_000499.1
SEQ ID NO. 159




FGA


 


160.
DNFPQSL
690-696
NP_000710.3
SEQ ID NO. 160




CACNA1C


 


161.
GLTDVILYH
269-277
NP_006363.3
SEQ ID NO. 161




SYNCRIP


 


162.
AALVASGVALY
247-257
NP_002557.2
SEQ ID NO. 162




P2RY11


 


163.
AEIRHVLVTL
107-116
NP_066299.2
SEQ ID NO. 163




MYL6


 


164.
AEPEEVEVL
10-18
NP_150638.1
SEQ ID NO. 164




PGR1


 


165.
AIIDHIFASK
256-265
NP_787062
SEQ ID NO. 165




KIS


 


166.
ALLDGSNVVFK
48-58
NP_055075.1
SEQ ID NO. 166




HKE2


 


167.
AMLDTVVFK
302-310
NP_005796.1
SEQ ID NO. 167




PSMD14


 


168.
APARLFALL
2-10
NP_002990.2
SEQ ID NO. 168




SDC4


 


169.
AVNAHSNILK
248-257
NP_006830
SEQ ID NO. 169




IMMT


 


170.
APRPGVLLL
8-16
NP_000492
SEQ ID NO. 170




ELN


 


171.
EAFPLRVID
749-757
NP_006113.1
SEQ ID NO. 171




MAN2A2


 


172.
GVADKILKK
211-219
NP_004679.1
SEQ ID NO. 172




NMI


 


173.
AVFPKPFVEK
189-198
NP_055474.2
SEQ ID NO. 173




KIAA0377


 


174.
VVYVGGILTK
258-267
NP_003351.2
SEQ ID NO. 174




UGT8


 


175.
HLEDIVRQK
1751-1759
XP_376178.1
SEQ ID NO. 175




TRIP12


 


176.
VILYLVILSY
207-216
XP_372460.1
SEQ ID NO. 176




LOC390323


 


177.
SLLSLVTGLK
reading frame +3
CD1OS81S
SEQ ID NO. 177




Symbol does not




exist; Gene type:




expressed sequence




tag


 


178.
QTYVGITEK
687-695
NP_054733.2
SEQ ID NO. 178




U5-200KD


 


179.
HEDKIRVVL
210-218
NP_055416.2
SEQ ID NO. 179




EHD2


 


180.
QISIPFLLK
208-216
AAH01979
SEQ ID NO. 
180




C9orf88


 


181.
GLMGFIVYK
29-37
NP_004885.1
SEQ ID NO. 181




C14orf2


 


182.
FADQEVRSL
950-958
NP_002636.1
SEQ ID NO. 182




PIK3C2A


 


183.
IVALILSTK
147-155
NP_001685.1
SEQ ID NO. 183




ATP6V0C


 


184.
GTYAPAEVPK
22-31
NP_001344.2
SEQ ID NO. 184




AKR1C1


 


185.
GTMTGMLYK
161-169
NP_006318.1
SEQ ID NO. 185




TIMM23


 


186.
SLAEILLKK
439-447
NP_006381.1
SEQ ID NO. 186




IPO8


 


187.
KLTYIYIQK
Reading frame +1
AA295205
SEQ ID NO. 
187




Symbol does not




exist; Gene type:




expressed sequence




tag


 


188.
KLLNYAPLEK
58-67
NP_055427
SEQ ID NO. 188




POLR2L


 


189.
GTLPHPLQR
182-190
NP_001029.1
SEQ ID NO. 189




SCNN1A


 


190.
GLYEFFRAK
680-688
NP_006378.2
SEQ ID NO. 190




CHERP


 


191.
KEPEINTIL
226-234
NP_689939.1
SEQ ID NO. 191




FLJ34588


 


192.
HASDRIIAL
330-338
NP_001055.1
SEQ ID NO. 192




TKT


 








Sequences of RCC098













193.
RPTLWAAAL
5-13
NP_000589.1
SEQ ID NO. 193





IGFBP3


 


194.
APSPRPLSL
11-19
NP_778148.1
SEQ ID NO. 194




C19orf28


 


195.
ASDFITKMDY
362-371
NP_000168.1
SEQ ID NO. 195




GSN


 


196.
EERVINEEY
13-21
NP_005601.1
SEQ ID NO. 196




RBBP4


 


197.
ATGSWDSFLK
328-337
NP_002065.1
SEQ ID NO. 197




GNB1


 


198.
RMFDMGFEY
411-419
NP_031398.2
SEQ ID NO. 198




DDX42


 


199.
APLLRWVL
265-272
NP_002124.1
SEQ ID NO. 199




HMOX1


 


200.
ALRPSTSRSLY
43-53
NP_003371.1
SEQ ID NO. 200




VIM


 


201.
RQIPYTMMK
225-233
NP_002626.1
SEQ ID NO. 201




SLC25A3


 


202.
AETHIVLLF
267-275
NP_115497.3
SEQ ID NO. 202




DKFZpS64K142


 


203.
RVHAYIISY
305-313
NP_055416.2
SEQ ID NO. 203




EHD2


 


204.
AVIVLVENFYK
11-21
NP_525127.1
SEQ ID NO. 204




S100A16


 


205.
SEELLREHY
6169
NP_002504.2
SEQ ID NO. 205




NME3


 


206.
RADGNFLLY
368-376
XP_047214.6
SEQ ID NO. 206




KIAA0930


 


207.
SEFTGVWKY
83-91
NP_037364.1
SEQ ID NO. 207




PDCD6


 


208.
SIDRTVMYY
389-397
NP_000332.1
SEQ ID NO. 208




SLC3A1


 


209.
ETDLLDIRSEY
463-473
NP_001148.1
SEQ ID NO. 209




ANXA11


 


210.
ESYEALPQH
397-405
NP_001370.1
SEQ ID NO. 210




DNMT1


 


211.
SEEEIREAF
82-90
NP_001734.1
SEQ ID NO. 211




CALM2


 


212.
KVMQQNLVY
329-337
NP_006362.1
SEQ ID NO. 212




CRTAP


 


213.
DEKSIITY
262-269
NP_003119.1
SEQ ID NO. 213




SPTBN1


 


214.
EEIEGFRY
421-428
NP_061955.1
SEQ ID NO. 214




DDX56


 


215.
MENLFINRF
186-194
NP_000689.1
SEQ ID NO. 215




ALOX5


 


216.
MEKIWHHTF
82-90
NP_001092.1
SEQ ID NO. 216




ACTB


 


217.
MEHAMETMMF
5-14
NP_002957.1
SEQ ID NO. 217




S100A10


 


218.
EEIFNLKF
353-542
NP_001509.2
SEQ ID NO. 218




GTF2I


 


219.
LVLMVLYLI
153-161
NP_660150.1
SEQ ID NO. 219




PIGM


 


220.
EELQQKVSY
285-293
NP_003141.2
SEQ ID NO. 220




STAT3


 


221.
LRVAPEEHPVL
94-104
NP_001092.1
SEQ ID NO. 221




ACTB


 


222.
DGHLFQVEY
13-21
NP_002783.1
SEQ ID NO. 222




PSMA7


 


223.
LAELAHREY
1422
NP_003596.2
SEQ ID NO. 223




OGT


 


224.
NEADVHGIYF
651-660
NP_000087.1
SEQ ID NO. 224




CP


 


225.
KVFQEPLFY
114-122
NP_001903.1
SEQ ID NO. 225




CTSL


 


226.
GVLAWVKEK
171-179
NP_004212.3
SEQ ID NO. 226




NK4


 


227.
HEALLYYVL
738-746
NP_056002.1
SEQ ID NO. 227




KIAA0746


 


228.
HEMIILKL
3489-3496
XP_290768.3
SEQ ID NO. 228




KIAA1554


 


229.
IVPANFPSL
443-451
NP_116212.3
SEQ ID NO. 229




C9orf3


 


230.
HLDLGILYY
162-170
NP_001373.2
SEQ ID NO. 230




DPAGT1


 


231.
ITDSAGHILY
76-85
NP_006818.2
SEQ ID NO. 231




TMP21


 


232.
HTDDPLTWDY
267-276
NP_060898.1
SEQ ID NO. 232




HCA66


 


233.
IARNLTQQL
313-321
NP_001113.2
SEQ ID NO. 233




ADFP


 


234.
IDQTALAVY
1087-1095
NP_003282.1
SEQ ID NO. 234




TPP2


 


235.
LEDVVIERY
41-49
NP_068758.2
SEQ ID NO. 235




FKBP10


 


236.
QIASFILLR
316-324
NP_060796.1
SEQ ID NO. 236




HIMAP4


 


237.
DEHYILIF
550-557
NP_078862.2
SEQ ID NO. 237




OSBPL9


 


238.
DEIGLPKIFY
124-133
NP_003861.1
SEQ ID NO. 238




IQGAP1


 


239.
DEIVRINGY
132-140
NP_005700.1
SEQ ID NO. 239




USH1C


 


240.
DEKLLYDTF
112-120
NP_005841.1
SEQ ID NO. 240




SF3B4


 


241.
RIIEETLALK
9-18
NP_005722.1
SEQ ID NO. 241




ARPC2


 


242.
GTDELRLLY
107-115
NP_112483.1
SEQ ID NO. 242




FLJ12525


 


243.
DELEIIEGMKF
209-219
NP_002147.2
SEQ ID NO. 243




HSPD1


 


244.
QVDPLSALKY
649-658
NP_037387.2
SEQ ID NO. 244




MKLN1


 


245.
DELHYLEVY
72-80
NP_060676.2
SEQ ID NO. 245




VPS35


 


246.
EEFELLGKAY
81-90
NP_003743.1
SEQ ID NO. 246




EIF3S8


 


247.
QLEDGRTLSDY
49-59
NP_061828.1
SEQ ID NO. 247




UBB


 


248.
DEFLWREQF
42-50
NP_061871.1
SEQ ID NO. 248




FBXW5


 


249.
DEMLSRGF
185-192
NP_001407.1
SEQ ID NO. 249




EIF4A1


 


250.
DEPLLKHWEF
196-205
NP_061984.1
SEQ ID NO. 250




HLA-DRA


 


251.
PSRDSLPLPV
418-427
NP_056412.2
SEQ ID NO. 251




GPSM1


 


252.
NLRETNLDSLP
422-432
NP_003371.1
SEQ ID NO. 252




VIM


 


253.
DEVKFLTVL
191-199
NP_001144.1
SEQ ID NO. 253




ANXA4


 


254.
NEVEKIMEY
440-448
NP_114130.3
SEQ ID NO. 254




RSHL2


 


255.
DEVQVVRGHY
53-62
NP_000978.1
SEQ ID NO. 255




RPL26


 


256.
DEWLKPELF
296-304
NP_057038.1
SEQ ID NO. 256




CGI-26


 


257.
DEYSLVREL
125-133
NP_006280.2
SEQ ID NO. 257




TLN1


 


258.
NEFEATQKL
343-351
NP_005375.1
SEQ ID NO. 258




NFIL3


 


259.
DELQQPLEL
704-712
NP_005410.1
SEQ ID NO. 259




STAT2


 


260.
DVVMTQSPLSL
20-30
S40322
SEQ ID NO. 260




IGKV@


 


261.
SEREAIEVF
358-366
NP_004111
SEQ ID NO. 261




GBP2


 


262.
RYFYHQEEY
21-29
CAA09468
SEQ ID NO. 262




HLA-DRB1


 


263.
TSALPIIQK
63-71
NP_001113.2
SEQ ID NO. 263




ADFP


 


264.
RVQEAVESMVK
8-18
AAH14975
SEQ ID NO. 264




FLJ14668


 


265.
TVMELVKIIYK
237-247
NP_057111.1
SEQ ID NO. 265




LACTB2


 


266.
RLLQKVLAY
103-111
BAA91493
SEQ ID NO. 266




FLJ10211


 


267.
RIHFPLATY
264-272
NP_006073
SEQ ID NO. 267




K-ALPHA-1


 


268.
VGGLKNTLVHRL
279-290
NP_695000.1
SEQ ID NO. 268




FLJ31579


 


269.
QAQADSLTVY
679-688
AAP97251.1
SEQ ID NO. 269




PCDHB5


 


270.
VLDPYLLKY
34-42
NP_057053.1
SEQ ID NO. 270




MRPS17


 


271.
IFSPPFPLFY
83-92
AAK08108.1
SEQ ID NO. 271




FKSG63


 


272.
TELLLKEGF
260-268
NP_055205.1
SEQ ID NO. 272




SND1


 


273.
GLFEVGAGWIGK
235-246
NP_000405.1
SEQ ID NO. 273




HSD17B4


 


274.
YEYKFGFEL
97-105
NP_006463.2
SEQ ID NO. 274




TXNIP


 


275.
WPLWRLVSL
2-10
NP_001702.1
SEQ ID NO. 275




BGN


 


276.
YIDEQFERY
121-129
NP_004395.1
SEQ ID NO. 276




NEDD5


 


277.
YLDEKLALLNA
897-907
NP_003924.2
SEQ ID NO. 277




BAIAP3


 


278.
DEHLITFF
1248-1255
NP_054733.2
SEQ ID NO. 278




U5-200KD


 


279.
DDFHIYVY
234-241
NP_006708
SEQ ID NO. 279




SPIN


 


280.
APRTVLLLL
5-13
AAL30417.1
SEQ ID NO. 280




HLA-A, -B or -C


 


281.
APRTVALTALL
9-19
NP_002112
SEQ ID NO. 281




HLA-DPB1


 


282.
FTDVNSILRY
58-67
AAH58921
SEQ ID NO. 282




EPRS


 


283.
YSEEECRQY
61-69
NP_002061.1
SEQ ID NO. 283




GNAI2


 


284.
YSEKIVDMY
134-142
NP_002465.1
SEQ ID NO. 284




MYH11


 


285.
YTDLLRLFEY
68-77
NP_002700.1
SEQ ID NO. 285




PPP1CB


 


286.
YVDPQFLTY
341-349
NP_071763.2
SEQ ID NO. 286




PJA1


 


287.
HERTFLLEY
96-104
NP_067072.2
SEQ ID NO. 287




SNX6


 


288.
SSVPGVRLLQDSVDFSL
72-88
NP_003371.1
SEQ ID NO. 288




VIM


 


289.
SLLTSSKGQLQK
369-380
NP_001113.2
SEQ ID NO. 289




ADFP


 


290.
SPRENILVSL
281-290
NP_005054.2
SEQ ID NO. 290




SCD


 


291.
DEVDIKSRAAY
18-28
XP_051200.4
SEQ ID NO. 291




FTO


 


292.
TSPSQSLFY
154-162
AAH41787.1
SEQ ID NO. 292




SLC11A1


 


293.
YTETEPYHNY
392-401
NP_653205.2
SEQ ID NO. 293




LOC124245


 


294.
SSVPGVRLLQDSVDF
72-86
NP_003371.1
SEQ ID NO. 
294




VIM


 


295.
VALISPKDI
Reading frame −1
AC079587.4
SEQ ID NO. 
295




Symbol does not




exist; Gene type:




expressed sequence




tag


 


296.
STDKAEYTFY
332-341
NP_005340.2
SEQ ID NO. 296




RBPSUH


 


297.
VTEIFRQAF
250-258
BAA74907.1
SEQ ID NO. 297




GARNL1


 


298.
SVLSPLLNK
380-388
NP_004438.2
SEQ ID NO. 298




EPS8


 








Sequences of RCC100













299.
RAFSSLGLLK
615-624
NP_003352.1
SEQ ID NO. 299





UMOD


 


300.
FSKLRPLISK
243-252
NP_736609.1
SEQ ID NO. 300




PGBD3


 


301.
RTFTWLVGK
353-361
NP_203693.2
SEQ ID NO. 301




MYO1C


 


302.
KVANIILSY
1273-1281
NP_079413.2
SEQ ID NO. 302




FLJ21439


 


303.
TMLARLASA
21-29
NP_001888.1
SEQ ID NO. 303




CSPG4


 


304.
HELPLPHSV
39-47
NP_001421.2
SEQ ID NO. 304




EPAS1


 







Sequences of RCC103













305.
AVQRTLLEK
177-185
NP_002405.1
SEQ ID NO. 305





CD99


 


306.
ETRPAGDGTFQKW
256-268
NP_002107
SEQ ID NO. 306




HLA-A


 


307.
AVLSILPAIFQK
392-403
XP_084530.5
SEQ ID NO. 307




KIAA0033


 


308.
EIAGHIMEF
848-856
NP_055491.1
SEQ ID NO. 308




PUM1


 


309.
ELIRTIMGW
131-139
NP_004315.1
SEQ ID NO. 309




BAX


 


310.
EVFPLKVFGY
45-54
AAH29439
SEQ ID NO. 310




ZNF258


 


311.
ATPTSPIRVK
856-865
NP_001447.1
SEQ ID NO. 311




FLNA


 


312.
AVLYQPLFDK
107-116
NP_004528.1
SEQ ID NO. 312




NAP1L1


 


313.
EVVDFIQSKI
451-460
NP_817092
SEQ ID NO. 313




PPM1G


 


314.
AVQEFGLARFK
142-152
NP_037369.1
SEQ ID NO. 314




PX19


 


315.
EAIQDLWQW
282-290
NP_002511.1
SEQ ID NO. 315




NPM1


 


316.
GVIRSLMAF
60-68
NP_036558.2
SEQ ID NO. 316




SF3B3


 


317.
HIISGTCASW
241-250
NP_006463.2
SEQ ID NO. 317




TXNIP


 


318.
GVIDVITKTW
261-270
NP_110407.2
SEQ ID NO. 318




MFTC


 


319.
GVIDLIFEK
600-608
NP_004944.2
SEQ ID NO. 319




EIF4G1


 


320.
GVCHIFASF
29-37
NP_005608.1
SEQ ID NO. 320




RBS14


 


321.
GTYVSSVPR
242-250
NP_002110.1
SEQ ID NO. 321




HLA-DOA


 


322.
GTAGLLEQWLK
329-339
NP_064572.1
SEQ ID NO. 322




DC12


 


323.
HVITGLLEHY
133-142
NP_612364.1
SEQ ID NO. 323




SCRN2


 


324.
GTADELVLHSW
176-186
NP_620149.1
SEQ ID NO. 324




LYPLAL1


 


325.
EIKEVILEF
873-881
NP_060154
SEQ ID NO. 325




VPS13C


 


326.
EEASLLHQF
741-749
NP_003119.1
SEQ ID NO. 326




SPTBN1


 


327.
KLFIGGLSF
15-23
NP_002127.1
SEQ ID NO. 327




HNRPA1


 


328.
DVVPAVRKW
134-142
NP_067027.1
SEQ ID NO. 328




MASA


 


329.
DVTGVVRQW
200-208
NP_000651.1
SEQ ID NO. 329




TGFB1


 


330.
DVKDYIQEY
2500-2508
XP_290768.3
SEQ ID NO. 330




KIAA554


 


331.
DVIDNDSWRLW
207-217
NP_006443.1
SEQ ID NO. 331




PAICS


 


332.
DVFSSKGMTRW
90-100
NP_803876.1
SEQ ID NO. 332




RASSF6


 


333.
DTVKKIESF
3197-3205
NP_006258.2
SEQ ID NO. 333




RANBP2


 


334.
DLPSNHVIDRW
211-221
NP_006100.2
SEQ ID NO. 334




SKB1


 


335.
DLIGHIVEF
726-734
NP_056132.1
SEQ ID NO. 335




PUM2


 


336.
DKESQLEAY
106-114
NP_872387.1
SEQ ID NO. 336




LOC284680


 


337.
EVIKLKGYTSW
240-250
NP_005557.1
SEQ ID NO. 337




LDHA


 


338.
GSSDVIIHR
519-527
XP_290536.2
SEQ ID NO. 338




KIAA542


 


339.
GTLDYILQR
158-166
XP_051200.4
SEQ ID NO. 339




FTO


 


340.
EVDKRVHMTW
326-335
NP_002808.2
SEQ ID NO. 340




PSMD13


 


341.
SVPYFLFQHW
197-206
NP_003092.3
SEQ ID NO. 341




SOAT1


 


342.
SVEEISTLVQK
93-103
NP_115488.2
SEQ ID NO. 342




MRPL43


 


343.
STFQQMWISK
352-361
NP_001604.1
SEQ ID NO. 343




ACTA2


 


344.
TTIPHALLTW
1533-1542
NP_006412.1
SEQ ID NO. 344




BIG1


 


345.
SAFLLLGLFK
419-428
NP_003181.3
SEQ ID NO. 345




TAPBP


 


346.
NIGDEALIGRW
637-647
NP_110428.2
SEQ ID NO. 346




MAGED4


 


347.
TVAFVPISGW
187-196
NP_001393.1
SEQ ID NO. 347




EEF1A1


 


348.
ETVNLRSLGF
1930-1939
XP_166300.3
SEQ ID NO. 348




AIM1


 


349.
MPKFSMPGF
72-80
BAC87652.1
SEQ ID NO. 349




AHNAK


 


350.
EVMEIMSRF
98-106
NP_006493.1
SEQ ID NO. 350




POLH


 


351.
EVMDVFLRF
695-703
XP_376724.1
SEQ ID NO. 351




CSG1cA-T


 


352.
RLQEALNLF
265-273
NP_000507.1
SEQ ID NO. 352




GNAS


 


353.
ETIDWKVFESW
174-184
NP_004346.1
SEQ ID NO. 353




CD74


 


354.
ELMEHGVVSW
39-48
NP_078988.1
SEQ ID NO. 354




ELMO3


 


355.
ASVAWAVLK
2-10
NP_387504.1
SEQ ID NO. 355




CASPR3


 


356.
SVSPVVHVR
73-81
NP_612403.2
SEQ ID NO. 356




LOC92906


 


357.
HVVDRDTEAW
27-36
NP_775898.2
SEQ ID NO. 357




FLJ35220


 


358.
ETITGLRVW
6493-6501
NP_004534.1
SEQ ID NO. 358




NEB


 


359.
RQLEDILSTY
77-86
NP_787048.1
SEQ ID NO. 359




DKFZp4S1J0118


 


360.
AIAQAESLRYK
98-108
NP_000996.2
SEQ ID NO. 360




RPS3


 


361.
GVLQLGNIVFK
345-355
NP_002464.1
SEQ ID NO. 361




MYH9


 


362.
EVINALKQTW
489-498
NP_006448.1
SEQ ID NO. 362




LIM


 


363.
STAAFFLLR
407-415
NP_001458.1
SEQ ID NO. 363




SLC37A4


 


364.
DIYNFPIHAF
177-186
NP_115898.2
SEQ ID NO. 364




LOC84549


 


365.
TVVERMLSNW
1398-1407
BAA21S71.1
SEQ ID NO. 365




PLXNB2


 


366.
TKPWFASQIPF
210-220
XP_293971.3
SEQ ID NO. 366




LOC345778


 








Sequences of RCC112













367.
GRVDFAYKF
111-119
NP_004418.2
SEQ ID NO. 367





PHC2


 


368.
GRDLTDYLM
182-190
NP_001605.1
SEQ ID NO. 368




ACTG1


 


369.
GRISITGVGF
101-110
NP_612501.3
SEQ ID NO. 369




MGC21644


 


370.
GRIVTLISF
262-70
NP_068779.1
SEQ ID NO. 370




MCL1


 


371.
GRLDLQYAKL
622-631
NP_000436.1
SEQ ID NO. 371




PLEC1


 


372.
GRTNLIVNY
18-26
NP_001410.2
SEQ ID NO. 372




ELAVL1


 


373.
RYFDTAVSR
5-13
AAC17722
SEQ ID NO. 373




HLA-A, -B or -C


 


374.
GRMVQVHEL
170-178
NP_006355.2
SEQ ID NO. 374




SEC23A


 


375.
FLDASGAKLDY
53-63
NP_055485.2
SEQ ID NO. 375




BZW1


 


376.
ATDYHVRVY
348-356
NP_073600.2
SEQ ID NO. 376




FAD104


 


377.
ARLBWAGQL
624-632
NP_065385.2
SEQ ID NO. 377




PBXIP1


 


378.
YGMPRQIL
192-199
NP_003555.1
SEQ ID NO. 378




TAGLN2


 


379.
GRLLVATTF
385-393
NP_002152.1
SEQ ID NO. 379




IARS


 


380.
AGGDWFTSR
136-144
NP_055040.2
SEQ ID NO. 380




PPP2R1A


 


381.
GRAPISNPGM
179-188
NP_002937
SEQ ID NO. 381




RPA2


 


382.
GRMENLASYR
308-317
NP_005389
SEQ ID NO. 382




PPP1R3C


 


383.
VLPKSRVEL
89-97
BAA81787
SEQ ID NO. 383




HLA-DOA


 


384.
DAKIRIFDL
28-36
NP_006004.1
SEQ ID NO. 384




RBL10


 


385.
GRAMVARLGL
2-11
NP_037362.1
SEQ ID NO. 385




CD24


 


386.
FIDASRLVY
612-620
NP_001894.1
SEQ ID NO. 386




CTNNA1


 


387.
DPMKARVVL
21-29
NP_003124.1
SEQ ID NO. 387




SRP9


 


388.
FRFDPQFAL
77-85
XP_371812
SEQ ID NO. 388




HLA-DQA1


 


389.
DTDHYFLRY
165-173
NP_057021.2
SEQ ID NO. 389




PIGT


 


390.
ELLIRKLPF
60-68
NP_003484.1
SEQ ID NO. 390




HIST3H3


 


391.
EAFVRHIL
142-149
NP_066299.2
SEQ ID NO. 391




MYL6


 


392.
RYFDTAMSR
5-13
AAB48498.1
SEQ ID NO. 392




HLA-A, -B or -C


 


393.
GRVFIISKY
416-424
NP_689971
SEQ ID NO. 393




FLJ31657


 


394.
TFRPAAMLVER
154-164
NP_002283.2
SEQ ID NO. 394




LAMB2


 


395.
YLLEKSRAI
257-265
NP_002464.1
SEQ ID NO. 395




MYH9


 


396.
LSDLGKLSY
353-361
NP_115564.1
SEQ ID NO. 396




MYST1


 


397.
VTDSIRDEY
258-266
NP_005681.1
SEQ ID NO. 397




DNM1L


 


398.
LTDRELEFY
567-575
NP_001110.2
SEQ ID NO. 398




ADD1


 


399.
LTDRGVMSY
252-260
NP_001562.1
SEQ ID NO. 399




IRF3


 


400.
KGLSVFLNR
527-535
NP_002501.1
SEQ ID NO. 400




GPNMB


 


401.
VTDNRAFGY
128-136
NP_001334.1
SEQ ID NO. 401




DAB2


 


402.
STDVSDLLHQY
257-267
NP_004150.1
SEQ ID NO. 402




PSMB8


 


403.
RSLPFFSAR
135-143
NP_067033.1
SEQ ID NO. 403




TRAPPC1


 


404.
YRFMGTEAY
378-386
NP_000332.1
SEQ ID NO. 404




SLC3A1


 


405.
MPLLRQEEL
394-402
NP_055416.2
SEQ ID NO. 405




EHD2


 


406.
VTEIDQDKY
2380-2388
NP_001447.1
SEQ ID NO. 406




FLNA


 


407.
MRHLGAFLF
1-9
NP_000346.2
SEQ ID NO. 407




TCN2


 


408.
TTEESLRNYY
20-29
NP_002128.1
SEQ ID NO. 408




HNRPA2B1


 


409.
MRTSYLLLF
1-9
NP_005209.1
SEQ ID NO. 409




DEFB1


 


410.
TVDQVKDLY
882-890
NP_000087.1
SEQ ID NO. 410




CP


 


411.
MRYVASYLL
1-9
NP_000995.1
SEQ ID NO. 411




RPLP2


 


412.
VGLIRNLAL
511-519
NP_001895.1
SEQ ID NO. 412




CTNNB1


 


413.
GRLDAVLQR
317-325
NP_002666.1
SEQ ID NO. 413




PML


 


414.
LLDQGQLNKY
421-430
NP_004850.1
SEQ ID NO. 414




CLTC


 


415.
NRFAGFGIGL
98-107
NP_620128.1
SEQ ID NO. 415




LOC91137


 


416.
KRLGTLVVTY
305-314
NP_443173.2
SEQ ID NO. 416




GBP4


 


417.
KRGDVIYIL
319-327
NP_003921.2
SEQ ID NO. 417




SCAP2


 


418.
SRFDIBLGL
1103-1111
NP_056969.2
SEQ ID NO. 418




PCF11


 


419.
STDPSVLGKY
101-110
NP_005515.1
SEQ ID NO. 419




HES1


 


420.
SRFLKSDLF
130-138
NP_002916.1
SEQ ID NO. 420




RGS10


 


421.
VQKPSYYVR
211-219
NP_001113.2
SEQ ID NO. 421




ADFP


 


422.
SRISLPLPNF
409-418
NP_003371.1
SEQ ID NO. 422




VIM


 


423.
LRSGLPLLL
231-239
NP_004790.1
SEQ ID NO. 423




MADHIP


 


424.
SFKDYIQER
330338
NP_005230.1
SEQ ID NO. 424




ETS2


 


425.
HTQGPVDGSLY
104-114
NP_073585.6
SEQ ID NO. 425




TENS1


 


426.
STDKFKTDFY
271-280
NP_006824.2
SEQ ID NO. 426




COPS6


 








Sequences of RCC115













427.
GSHSMRYFF
25-33
NP_002107
SEQ ID NO. 427





HLA-A


 


428.
GSHSMRYFFT
25-34
NP_002107
SEQ ID NO. 428




HLA-A


 


429.
GSHSMRYFH
25-33
I37515
SEQ ID NO. 429




HLA-B


 


430.
AAILGMHNL
135-143
NP_055362.1
SEQ ID NO. 430




TMOD3


 


431.
KLDPTKTTL
275-283
NP_006087.2
SEQ ID NO. 431




NDRG1


 


432.
FVHDLVLYL
783-791
NP_001826.1
SEQ ID NO. 432




CLICL1


 


433.
FVHDLVL
783-789
NP_001826.1
SEQ ID NO. 433




CLICL1


 


434.
VLIPKLPQL
134-142
NP_644809.1
SEQ ID NO. 434




ORMDL3


 


435.
NEITIPVTF
177-185
NP_001531.1
SEQ ID NO. 435




HSPB1


 


436.
YLADFLLTK
255-263
NP_006623.1
SEQ ID NO. 436




SLC17A3


 


437.
YLIPLLERL
139-147
NP_004388.1
SEQ ID NO. 437




DDX6


 


438.
NEVVTREY
18-25
NP_000984.1
SEQ ID NO. 438




RPL31


 


439.
DEFKIGELF
145-153
NP_008835
SEQ ID NO. 439




PRKDC


 


440.
IQRTPKIQVYS
21-31
NP_004039.1
SEQ ID NO. 440




B2M


 


441.
LTGPVMPVR
150-158
NP_000968.2
SEQ ID NO. 441




RPL13


 


442.
AVAIKAMAK
146-154
NP_001961.1
SEQ ID NO. 442




EIF5A


 


443.
FVQMMTAK
142-149
NP_008819.1
SEQ ID NO. 443




CALM1


 


444.
ATDPNILGR
4111-4119
NP_008835.5
SEQ ID NO. 444




PRKDC


 


445.
LLLLSIVIL
212-220
NP_001391.2
SEQ ID NO. 445




EDG1


 


446.
KLPNFGFVVF
376-385
NP_005745.1
SEQ ID NO. 446




G3BP


 


447.
KLSEIDVAL
174-182
NP_079478.1
SEQ ID NO. 447




EFHD1


 


448.
LAALPHSCL
5-13
NP_003608.1
SEQ ID NO. 448




RGS5


 


449.
YSIITPNILRL
26-36
NP_000055.1
SEQ ID NO. 449




C3


 


450.
ALPSRILLWK
2-11
NP_115724.1
SEQ ID NO. 450




MGC3047


 


451.
VKGFYPSDIAVE
247-258
AAB59393.1
SEQ ID NO. 451




IGHG2


 


452.
FLLDLSRSV
92-100
NP_005290.1
SEQ ID NO. 452




GPR31


 


453.
IIYKGGTSR
545-553
NP_000168.1
SEQ ID NO. 453




GSN


 


454.
IVADHVASY
3-11
AAC41957
SEQ ID NO. 454




MHC class II


 


455.
EVGGEALGRLL
23-33
NP_000509.1
SEQ ID NO. 455




HBB


 


456.
RTGPPMGSRF
175-184
NP_071496.1
SEQ ID NO. 456




WBSCR1


 


457.
RQIQESVTF
1305-1313
NP_001139.2
SEQ ID NO. 457




ANK2


 


458.
RVAPEEHPV
95-103
NP_001092.1
SEQ ID NO. 458




ACTB


 


459.
TLADLLALR
1433-1441
NP_003768.1
SEQ ID NO. 459




DNAH11


 


460.
RVAPEEHPVLLT
95-106
NP_001092.1
SEQ ID NO. 460




ACTB


 


461.
TLADIIARL
1487-1495
XP_370756.2
SEQ ID NO. 461




KIAA1305


 


462.
RWEDGSPLNF
142-151
NP_005801.2
SEQ ID NO. 462




KLRG1


 


463.
YEVSQLKD
468-475
NP_060705.1
SEQ ID NO. 463




CNDP2


 


464.
YRDIPELQGF
663-672
NP_076417
SEQ ID NO. 464




AACS


 


465.
YVDGTQFVRF
51-60
BAA04965
SEQ ID NO. 465




HLA-A, -B or -C


 


466.
SLLDEFYKL
184-192
NP_005889.3
SEQ ID NO. 466




M11S1


 


467.
HGIDPTGTY
28-36
NP_006078.2
SEQ ID NO. 467




TUBB5


 


468.
SLDKFLASVSTVL
125-137
NP_000549.1
SEQ ID NO. 468




HBA1


 


469.
SIGERDLIFH
289-298
NP_003911.1
SEQ ID NO. 469




TIMELESS


 


470.
SITSVFITK
1788-1796
NP_003487.1
SEQ ID NO. 470




TRRAP


 


471.
FGEHLLESDLF
28-38
NP_001876.1
SEQ ID NO. 471




CRYAB


 


472.
FLDPIKAYL
76-84
NP_056049.3
SEQ ID NO. 472




GPR116


 


473.
FLADPSAFVAA
268-278
NP_000993.1
SEQ ID NO. 473




RPLP0


 


474.
ITAPPSRVL
20-28
NP_005054.2
SEQ ID NO. 474




SCD


 


475.
VLDELKNMKC
170-179
NP_055191.1
SEQ ID NO. 475




CYFIP2


 


476.
LLGPRLVLA
23-31
NP_006818.2
SEQ ID NO. 476




TMP21


 


477.
IIMPHNIYL
251-259
NP_000569.2
SEQ ID NO. 477




SLC11A1


 


478.
LVRMVLNG
144-151
NP_034990
SEQ ID NO. 478




MYL6


 


479.
RLYGPSSVSF
133-142
NP_001226.2
SEQ ID NO. 479




SERPINH1


 


480.
FEAPIKLVF
236-244
NP_110416.1
SEQ ID NO. 480




HM13


 


481.
IQPGAVKVY
1472-1480
NP_000055.1
SEQ ID NO. 481




C3


 


482.
VLAEVPTQL
501-509
NP_003906.1
SEQ ID NO. 482




CPNE1


 


483.
IMRAGMSSL
521-529
NP_001753.1
SEQ ID NO. 483




CCT6A


 


484.
VEFSSGLKGMSL
96-107
NP_004037.1
SEQ ID NO. 484




ATP5A1


 


485.
ILNPDNSFEIL
241-251
NP_001737.1
SEQ ID NO. 485




CANX


 


486.
VALEFALHL
344-352
NP_612384.1
SEQ ID NO. 486




CABLES1


 


487.
TVAVPLVGK
22-30
NP_077271.1
SEQ ID NO. 487




MGC3067


 


488.
TLSDLRVYL
121-129
NP_542763.1
SEQ ID NO. 488




C20Orf139


 


489.
TLIDIMTRF
35-43
NP_000179.1
SEQ ID NO. 489




HK1


 








Sequences of RCC116













490.
HDFPRALIF
64-72
AAH22188
SEQ ID NO. 490





CG018


 


491.
GSHSMRYF
25-32
BAA04965
SEQ ID NO. 491




HLA-A, -B or -C


 


492.
SLMDHTIPEV
289-298
NP_005616.1
SEQ ID NO. 492




SDCBP


 


493.
SGVHTFPAVLQ
155-165
AAO22172
SEQ ID NO. 493




Ig heavy chain


 


494.
FLVTVIHTL
1065-1073
NP_005752.1
SEQ ID NO. 494




PLXNC1


 


495.
TDGKVFQF
24-31
NP_000977.1
SEQ ID NO. 495




RPL24


 


496.
YDLLRNTNF
246-254
NP_001387.2
SEQ ID NO. 496




DYRK1A


 


497.
ILYPKTLFL
138-146
NP_000935.1
SEQ ID NO. 497




PPP3CA


 


498.
MRYVASYL
1-8
NP_000995.1
SEQ ID NO. 498




RPLP2


 


499.
FIWENIHTL
3725-3733
NP_056363.2
SEQ ID NO. 499




BPAG1


 


500.
RELPAWVSF
125-133
NP_056107.1
SEQ ID NO. 500




MBC2


 


501.
QDLNRIFPL
81-89
NP_002718.2
SEQ ID NO. 501




PRG1


 


502.
RDSIVAEL
97-104
NP_009194.2
SEQ ID NO. 502




COPE


 


503.
ADVLKVEVF
130-138
NP_002203.1
SEQ ID NO. 503




ITGB4BP


 


504.
YDSIIYRM
335-342
NP_005756.2
SEQ ID NO. 504




ATP6AP2


 


505.
AMNPVEHPF
203-211
NP_000964.1
SEQ ID NO. 505




RPL8


 


506.
SELIRNVTL
126-134
NP_004238.2
SEQ ID NO. 506




U5-116KD


 


507.
QDVARVLGF
117-125
NP_006020.3
SEQ ID NO. 507




PNMA1


 


508.
SDHIHIIAL
215-223
NP_060140.1
SEQ ID NO. 508




OTUB1


 


509.
ADSLRLQQL
781-789
NP_003118.1
SEQ ID NO. 509




SPTAN1


 


510.
LLDIRSEY
466-473
NP_001148.1
SEQ ID NO. 510




ANXA11


 


511.
VLFGLLREV
663-671
NP_054722.2
SEQ ID NO. 511




DHX38


 


512.
VAVGRALYY
510-518
NP_001914.2
SEQ ID NO. 512




DDB1


 


513.
MRFLAATFL
1-9
NP_006423.1
SEQ ID NO. 513




NPC2


 


514.
YTDPEVFKY
398-406
NP_000952.1
SEQ ID NO. 514




PTGIS


 


515.
HDFLKYDFF
232-240
NP_149351.1
SEQ ID NO. 515




SURF4


 


516.
AIDQLHLEY
525-533
NP_004915.2
SEQ ID NO. 516




ACTN4


 


517.
SDLERVTSL
316-324
NP_078843.2
SEQ ID NO. 517




FLJ21616


 


518.
TLLPLRVFL
128-136
NP_699196.1
SEQ ID NO. 518




FLJ90013


 


519.
YSIITPNILR
26-35
NP_000055.1
SEQ ID NO. 519




C3


 


520.
FELQRNFQL
19-27
NP_057246.2
SEQ ID NO. 520




ING4


 


521.
LDLQRNYIF
186-194
NP_940967.1
SEQ ID NO. 521




UNQ3030


 


522.
RRLDPIPQL
56-64
NP_057211.4
SEQ ID NO. 522




MGC8721


 


523.
SLPIKESEIIDF
85-96
NP_002943.2
SEQ ID NO. 523




RPS2


 


524.
TELLRYYML
292-300
NP_055241.1
SEQ ID NO. 524




SNX5


 


525.
FIYHGEVPQA
254-263
NP_000237.1
SEQ ID NO. 525




MHC2TA


 


526.
AEMLRSISF
217-225
NP_001315.1
SEQ ID NO. 526




CSTF1


 


527.
RLQEDPPVGV
15-24
NP_003328.1
SEQ ID NO. 527




UBE2B


 


528.
AELERAAAL
465-473
NP_689813.1
SEQ ID NO. 528




FLJ35453


 


529.
YTDKIDRY
107-114
NP_003262.1
SEQ ID NO. 529




TM4SF7


 


530.
FLLPDVIRI
329-337
NP_060671.2
SEQ ID NO. 530




TBC1D13


 


531.
VELPHINLL
169-177
NP_060536.2
SEQ ID NO. 531




FLJ10349


 


532.
VMLDVPIRL
725-733
NP_004832.1
SEQ ID NO. 532




RASAL2


 


533.
SLLENLEKI
209-216
NP_112604.1
SEQ ID NO. 533




HNRPC


 


534.
YADPVNAHY
226-234
NP_005147.3
SEQ ID NO. 534




ROD1


 


535.
AELLRGLSL
165-173
NP_036293.1
SEQ ID NO. 535




FBXL5


 


536.
TTEVHPELY
51-59
NP_057050.1
SEQ ID NO. 536




SDBCAG84


 


537.
RETNLDSLP
424-432
NP_003371.1
SEQ ID NO. 537




VIM


 


538.
ELEDSTLRY
543-551
NP_000436.1
SEQ ID NO. 538




PLEC1


 








Sequences of RCC130













539.
FLDIYIFL
84-91
XP_372703.1
SEQ ID NO. 539





LOC390875


 


540.
TYTDRVFFL
1282-1290
BAA21S71.1
SEQ ID NO. 540




PLXNB2


 


541.
SPHLANYFYF
147-156
BAC87422
SEQ ID NO. 541




Symbol does not




exist; Gene type:




unnamed protein




product


 


542.
SPRLPVGGF
1921-1929
XP_376178.1
SEQ ID NO. 542




TRIP12


 


543.
KLLDKVQAYS
9-18
NP_000156.1
SEQ ID NO. 543




GJA1


 


544.
AYQHLFYLL
955-963
NP_839943.2
SEQ ID NO. 544




IQGAP3


 


545.
KYILLMDIIA
148-157
NP_005987.2
SEQ ID NO. 545




TBX3


 


546.
RYSSMAASF
82-90
NP_005755.1
SEQ ID NO. 546




MAP17


 


547.
SPRAAEPVQL
397-406
NP_001207.1
SEQ ID NO. 547




CA9


 


548.
IYTSSVNRL
535-543
NP_004757.1
SEQ ID NO. 548




COPB2


 


549.
LYPQFMFHL
576-584
NP_006355.2
SEQ ID NO. 549




SEC23A


 


550.
RYIPTAAAF
415-423
NP_037468.1
SEQ ID NO. 550




SEC61A1


 


551.
EYIVKKIPV
237-245
NP_001406.1
SEQ ID NO. 551




EIF2S3


 


552.
SRVEAVYVL
13-21
NP_031391.1
SEQ ID NO. 552




PADI2


 


553.
MPRGVVVTL
851-859
NP_056197.1
SEQ ID NO. 553




HECTD1


 


554.
LPKPPGRGV
341-349
NP_036294.1
SEQ ID NO. 554




FBXL6


 


555.
RLWGEPVNL
1665-1673
NP_004643.2
SEQ ID NO. 555




USP9X


 


556.
RLLDVLAPL
14-22
NP_569712.1
SEQ ID NO. 556




COL18A1


 


557.
LYILSSHDI
474-482
NP_277041.1
SEQ ID NO. 557




FBXO24


 


558.
TPMGPGRTV
235-243
NP_006490.3
SEQ ID NO. 558




LGALS8


 


559.
GPPGTGKTDVAVQI
823-836
NP_055506.1
SEQ ID NO. 559




AQR


 


560.
NEIEDTFRQF
46-55
NP_004222.2
SEQ ID NO. 560




ATP6V1F


 


561.
EEIDLRSVGW
315-324
NP_112192.2
SEQ ID NO. 561




UNC93B1


 


562.
KYQKGFSLW
245-253
NP_055109.1
SEQ ID NO. 562




TRAM1


 


563.
VYPDGIRHI
519-527
NP_036558.2
SEQ ID NO. 563




SF3B3


 


564.
KFIDTTSKF
366-374
NP_005052.1
SEQ ID NO. 564




RPL3L


 


565.
FLDILNTLI
1729-1737
NP_001362.1
SEQ ID NO. 565




DNAH8


 


566.
KYITQGQLLQF
200-210
NP_068586.1
SEQ ID NO. 566




ELOVL5


 


567.
KYLSVQGQLF
344-353
NP_055156.1
SEQ ID NO. 567




MTCH1


 


568.
RYFDEPVEL
355-363
NP_055385.2
SEQ ID NO. 568




ARFGAP3


 


569.
KYDEIFYNL
452-460
NP_055416.2
SEQ ID NO. 569




EHD2


 


570.
SYIEHIFEI
61-69
NP_003759.1
SEQ ID NO. 570




PEA15


 


571.
KFIDPIYQVW
572-581
NP_060897.2
SEQ ID NO. 571




RRN3


 


572.
LGYTEGALLAL
1370-1380
NP_149045.2
SEQ ID NO. 572




PCDH15


 


573.
KYPSPFFVF
2-10
NP_085077.1
SEQ ID NO. 573




DHX9


 


574.
EYPDRIMNTF
158-167
NP_006077.1
SEQ ID NO. 574




TUBB4


 


575.
VYISEHEHF
107-115
NP_001285.1
SEQ ID NO. 575




CLPTM1


 


576.
KYFLKPEVL
167-175
NP_065843.2
SEQ ID NO. 576




KIAA1363


 








Sequence of JY













577.
GPALGRSFL
78-86
NP_001243.1
SEQ ID NO. 577





TNFSF7


 








Sequences of the control peptides













578.
ELAGIGILTV
26-35
NP_005502.1
SEQ ID NO. 578





MLANA




(modified A27 ->L)


 


579.
ILKEPVHGV
896-904
NP_057849.4
SEQ ID NO. 579




pol


 


580.
GILGFVFTL
58-66
S14616
SEQ ID NO. 580




Symbol does not




exist; Gene type:




matrix protein M1


 


581.
NLVPMVATV
495-503
P06725
SEQ ID NO. 581




Symbol does not




exist; Gene type:




pp65


 


582.
LLDFVRFMGV
284-293
P03204
SEQ ID NO. 582




Symbol does not




exist; Gene type:




EBNA6 nuclear




protein


 


583.
GLCTLVAML
259-267
NP_039857.1
SEQ ID NO. 583




Symbol does not




exist; Gene type:




Immediate-early




transactivator


 


584.
CLGGLLTMV
294-302
AAB59844.1
SEQ ID NO. 584




Symbol does not




exist; Gene type:




latent membrane




protein 2


 


585.
APRIVALTA
9-17
NP_002112
SEQ ID NO. 585




HLA-DPB1

## Claims

1. An isolated peptide consisting of:
(a) SEQ ID NO: 303; or
(b) SEQ ID NO: 303 with the proviso that:
(b1) not more than one additional amino acid is added at the N-terminus of SEQ ID NO: 303; and/or
(b2) not more than one additional amino acid is present at the C-terminus of SEQ ID NO: 303; and


the peptide being capable of binding to a molecule of human major histocompatibility complex (MHC) class I.

2. The peptide of claim 1 consisting of SEQ ID NO: 303.

3. A composition comprising the peptide of claim 1.

4. The composition of claim 3, wherein the peptide consists of SEQ ID NO: 303.

5. The composition according to claim 3 further comprising at least one pharmaceutically acceptable carrier, and/or at least one excipient, and/or at least one immunostimulatory substance.