Large-scale analysis of HLA peptides presented by HLA-Cw4

A large number of HLA-Cw4 (Cw *0402) peptides were purified, sequenced, and identified from breast and ovarian carcinoma cell lines. HLA-Cw4 molecules were expressed in these cells as soluble, secreted HLA (sHLA) and recovered from the growth medium. The peptides were separated by capillary reversed-phase HPLC and analyzed by tandem mass-spectrometry. The resulting peptides fit to some extent, but not completely, the known consensus of the Cw4 peptide-binding motif. Among the identified peptides, there are a few that originate from proteins of possible interest for cancer immunotherapy or diagnostics, including mucin-5B, ART-1, fatty acid synthase, putative prostate cancer tumor suppressor, DNA topoisomerase-1, and Rac1. This work demonstrates that large-scale identification of HLA peptides recovered from sHLA is an advantageous approach for establishing the HLA peptide consensus of different haplotypes and the identification of useful peptides for treatment of diseases such as cancer, viral, and autoimmune diseases.

[1]  K. Parker,et al.  Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. , 1994, Journal of immunology.

[2]  S Buus,et al.  Description and prediction of peptide-MHC binding: the 'human MHC project'. , 1999, Current opinion in immunology.

[3]  H. Rammensee,et al.  SYFPEITHI: database for MHC ligands and peptide motifs , 1999, Immunogenetics.

[4]  C. Townsend,et al.  Synthesis and antitumor activity of an inhibitor of fatty acid synthase. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  W. Klitz,et al.  High-resolution HLA class I typing in the CEPH families: analysis of linkage disequilibrium among HLA loci. , 2000, Tissue antigens.

[6]  M. Perrais,et al.  Aberrant expression of human mucin gene MUC5B in gastric carcinoma and cancer cells. Identification and regulation of a distal promoter. , 2001, The Journal of biological chemistry.

[7]  A. D. Jong.  Contribution of mass spectrometry to contemporary immunology. , 1998 .

[8]  M. Duffy,et al.  Metalloproteinases: role in breast carcinogenesis, invasion and metastasis , 2000, Breast Cancer Research.

[9]  J. Verweij,et al.  Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan. , 2002, Current cancer drug targets.

[10]  Mark Lindsey,et al.  Large-scale production of class I bound peptides: assigning a signature to HLA-B*1501 , 1997, Immunogenetics.

[11]  W. Isaacs,et al.  Structure and methylation-associated silencing of a gene within a homozygously deleted region of human chromosome band 8p22. , 1996, Genomics.

[12]  J. Holden,et al.  Elevations of DNA Topoisomerase I in Invasive Carcinoma of the Breast , 2001, The breast journal.

[13]  R. Henderson,et al.  Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. , 1994, Science.

[14]  Ilan Beer,et al.  Analysis of endogenous peptides bound by soluble MHC class I molecules: a novel approach for identifying tumor‐specific antigens , 2002, European journal of immunology.

[15]  C. Townsend,et al.  Synthesis and antitumor activity of an inhibitor of fatty acid synthase , 2000 .

[16]  大場 一生.  Two putative tumor suppressor genes on chromosome arm 8p may play different roles in prostate cancer , 2001 .

[17]  E. Lengyel,et al.  Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b , 2000, Oncogene.

[18]  S. Shichijo,et al.  A new tumor-rejection antigen recognized by cytotoxic T lymphocytes infiltrating into a lung adenocarcinoma. , 2000, Cancer research.

[19]  V. Gnau,et al.  Allele-specific peptide ligand motifs of HLA-C molecules. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Henderson,et al.  Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. , 1992, Science.

[21]  L. Witters,et al.  Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[22]  Mark Lindsey,et al.  Complexity among constituents of the HLA-B*1501 peptide motif , 1998, Immunogenetics.