title: Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas.
abstract: OBJECTIVE
  To elicit a long-lasting antitumor immune response, CD8+ and CD4+ T cells should be activated. We attempted to isolate HLA-DR-presented peptides directly from dissected solid tumors, in particular from renal cell carcinoma, to identify MHC class II ligands from tumor-associated antigens (TAA) for their use in peptide-based immunotherapy.
  
  
  METHODS
  Tumor specimens were analyzed by immunohistochemical staining for their HLA class II expression. HLA class II peptides were subsequently isolated and identified by mass spectrometry. Gene expression analysis was done to detect genes overexpressed in tumor tissue. Peptides from identified TAAs were used to induce peptide-specific CD4+ T-cell responses in healthy donors and in tumor patients.
  
  
  RESULTS
  In the absence of inflammation, expression of MHC class II molecules is mainly restricted to cells of the immune system. To our surprise, we were able to isolate and characterize hundreds of class II peptides directly from primary dissected solid tumors, especially from renal cell carcinomas, and from colorectal carcinomas and transitional cell carcinomas. Infiltrating leukocytes expressed MHC class II molecules and tumor cells, very likely under the influence of IFNgamma. Our list of identified peptides contains ligands from several TAAs, including insulin-like growth factor binding protein 3 and matrix metalloproteinase 7. The latter bound promiscuously to HLA-DR molecules and were able to elicit CD4+ T-cell responses.
  
  
  CONCLUSIONS
  Thus, our direct approach will rapidly expand the limited number of T-helper epitopes from TAAs for their use in clinical vaccination protocols.
authors.affiliation: Immatics Biotechnologies GmbH, University of Tübingen, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
authors.forename: Maria-Dorothea
authors.initials: MD
authors.lastname: Nastke
authors.forename: Cécile
authors.initials: C
authors.lastname: Gouttefangeas
authors.forename: Gitsios
authors.initials: G
authors.lastname: Gitsioudis
authors.forename: Oliver
authors.initials: O
authors.lastname: Schoor
authors.forename: Florian
authors.initials: F
authors.lastname: Altenberend
authors.forename: Margret
authors.initials: M
authors.lastname: Müller
authors.forename: Björn
authors.initials: B
authors.lastname: Krämer
authors.forename: Anna
authors.initials: A
authors.lastname: Missiou
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Dorothee
authors.initials: D
authors.lastname: Wernet
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006684:HLA-DR Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D012333:RNA, Messenger; D007371:Interferon-gamma