Method of epitope discovery

A method of epitope discovery comprising the steps of:

• choosing a target cell that is infected by a virus;
• identifying a proteasome activity of the target cell, wherein said proteasome is either a housekeeping proteasome or an immune proteasome;
• and
• selecting an epitope from a population of peptide fragments of an antigen associated with the target cell, wherein the fragments have a known or predicted affinity for a major histocompatibility complex class I receptor peptide binding cleft, wherein the epitope selected corresponds to a cleavage product associated with said proteasome activity of the target cell.

A method of epitope discovery comprising the steps of:

• choosing a target cell that is infected by an intracellular parasite, wherein the intracellular parasite is a bacterium, a protozoan, a fungus, or a prion;
• identifying a proteasome activity of the target cell, wherein said proteasome is either a housekeeping proteasome or an immune proteasome;
• and
• selecting an epitope from a population of peptide fragments of an antigen associated with the target cell, wherein the fragments have a known or predicted affinity for a major histocompatibility complex class I receptor peptide binding cleft, wherein the epitope selected corresponds to a cleavage product associated with said proteasome activity of the target cell.

A method of discovering an epitope comprising the steps of:

• providing a sequence from a target cell, wherein the sequence encodes or comprises a protein expressed in the target cell, wherein the target cell is a neoplastic cell;
• identifying a population of peptide fragments of the protein, wherein the protein is selected from the group consisting of MelanA (MART-I), gp100 (Pmel 17), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, CEA, RAGE, NY-ESO, SCP-1, Hom/Mel-40, PRAME, p53, H-Ras, HER-2/neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus antigens EBNA, human papillomavirus (HPV) antigens E6 and E7, TSP-180, MAGE-4, MAGE-5, MAGE-6, p185erbB2, p180erbB-3, c-met, nm-23H1, PSA, TAG-72-4, CAM 17.1, NuMa, K-ras, β-Catenin, CDK4, Mum-1, and p16, wherein members of the population of peptide fragments have a known or predicted affinity for a major histocompatibility complex class I receptor peptide binding cleft;
• and
• selecting either a housekeeping epitope or an immune epitope from the population of peptide fragments, based thin a proteasome that is active in the target cell, wherein the proteasome is a housekeeping proteasome or an in immune proteasome.

A method of discovering an epitope comprising the steps of:

• providing a sequence from a target cell, wherein the sequence encodes or comprises a protein expressed in the target cell, wherein the target cell is infected by a virus;
• identifying a population of peptide fragments of the protein, wherein members of the population of peptide fragments have a known or predicted affinity for a major histocompatibility complex class I receptor peptide binding cleft;
• and
• selecting either a housekeeping epitope or an immune epitope from the population of peptide fragments, based upon a proteasome that is active in the target cell, wherein the proteasome is a housekeeping proteasome or an immune proteasome.

A method of discovering an epitope comprising the steps of:

• providing a sequence from a target cell, wherein the sequence encodes or comprises a protein expressed in the target call, wherein the target cell is infected by an intracellular parasite, and wherein the intracellular parasite is a bacterium, a protozoan, a fungus, or a prion;
• identifying a population of peptide fragments of the protein, wherein members of the population of peptide fragments have a known or predicted affinity for a major histocompatibility complex class I receptor peptide binding cleft;
• and
• selecting either a housekeeping epitope or an immune epitope from the population of peptide fragments, based upon a proteasome that is active in the target cell, wherein the proteasome is a housekeeping proteasome or an immune proteasome.

A method of discoing an epitope comprising the steps of:

• providing a sequence from a target cell, wherein the sequence encodes or comprises a protein expressed in the target cell, wherein the target cell is an intracellular parasite;
• identifying a population of peptide fragments of the protein, wherein members of the population of peptide fragments have a known or predicted affinity for a major histocompatibility complex class I receptor peptide binding cleft, wherein the affinity is determined by an algorithm;
• and
• selecting either a housekeeping epitope or an immune epitope from the population of peptide fragments, based upon a proteasome that is active in the target cell, wherein the proteasome is a housekeeping proteasome or an immune proteasome.

A method of epitope discovery comprising the steps of:

• providing a neoplastic cell and a sequence, wherein the sequence comprises or encodes an antigen associated with the neoplastic cell, wherein the antigen is selected from the group consisting of MelanA (MART-I), gp100 (Pmel 17), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, CEA, RAGE, NY-ESO, SCP-1, Hom/Mel-40, PRAME, p53, H-Ras, HER-2/neu, BCR-ABL, EZA-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus antigens, EBNA, human papillomavirus (HPV) antigens E6 and E7, TSP-180, MAGE-4, MAGE-5, MAGE-6, p185erbB2, p180erbB-3, c-met, nm-23H1, PSA, TAG-72-4, CAM 17.1, NuMa, K-ras, β-Catenin, CDK4, Mum-1, and p16;
• identifying a population of peptide fragments of the antigen, wherein the population of peptide fragments is predicted to have an affinity for a major histocompatibility complex class I receptor peptide binding cleft;
• and
• selecting an epitope from the population of peptide fragments, wherein the epitope is determined by in vitro analysis to be a proteasome cleavage reaction product of a housekeeping proteasome or an immune proteasome active in the neoplastic cell.