PMID- 10601354 OWN - NLM STAT- MEDLINE DCOM- 20000128 LR - 20190508 IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 190 IP - 12 DP - 1999 Dec 20 TI - A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription. PG - 1793-800 AB - By stimulating blood lymphocytes from a renal cell carcinoma patient in vitro with the autologous tumor cells, we obtained cytolytic T lymphocyte (CTL) clones that killed several autologous and allogeneic histocompatibility leukocyte antigen (HLA)-B7 renal carcinoma cell lines. We identified the target antigen of these CTLs by screening COS cells transfected with the HLA-B7 cDNA and with a cDNA library prepared with RNA from the tumor cells. The antigenic peptide recognized by the CTLs has the sequence LPRWPPPQL and is encoded by a new gene, which we named RU2. This gene is transcribed in both directions. The antigenic peptide is not encoded by the sense transcript, RU2S, which is expressed ubiquitously. It is encoded by an antisense transcript, RU2AS, which starts from a cryptic promoter located on the reverse strand of the first intron and ends up on the reverse strand of the RU2S promoter, which contains a polyadenylation signal. This mechanism of antigen expression is unprecedented and further illustrates the notion that many peptides recognized by T cells cannot be predicted from the primary structure of the major product of the encoding gene. Antisense transcript RU2AS is expressed in a high proportion of tumors of various histological types. It is absent in most normal tissues, but is expressed in testis and kidney, and, at lower levels, in urinary bladder and liver. Short-term cultures of normal epithelial cells from the renal proximal tubule expressed significant levels of RU2AS message and were recognized by the CTLs. Therefore, this antigen is not tumor specific, but corresponds to a self-antigen with restricted tissue distribution. FAU - Van Den Eynde, B J AU - Van Den Eynde BJ AD - Ludwig Institute for Cancer Research, Brussels Branch, B-1200 Brussels, Belgium. vandeneynde@licr.ucl.ac.be FAU - Gaugler, B AU - Gaugler B FAU - Probst-Kepper, M AU - Probst-Kepper M FAU - Michaux, L AU - Michaux L FAU - Devuyst, O AU - Devuyst O FAU - Lorge, F AU - Lorge F FAU - Weynants, P AU - Weynants P FAU - Boon, T AU - Boon T LA - eng SI - GENBANK/AF181720 SI - GENBANK/AF181721 SI - GENBANK/AF181722 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, Neoplasm) SB - IM CIN - J Exp Med. 1999 Dec 20;190(12):1729-32. PMID: 10601348 MH - Amino Acid Sequence MH - Antigen Presentation/genetics MH - Antigens, Neoplasm/*genetics/*immunology MH - Base Sequence MH - Carcinoma, Renal Cell/genetics/*immunology MH - *Cytotoxicity, Immunologic MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Kidney Neoplasms/genetics/*immunology MH - Molecular Sequence Data MH - T-Lymphocytes, Cytotoxic/immunology MH - *Transcription, Genetic MH - Tumor Cells, Cultured PMC - PMC2195717 EDAT- 1999/12/22 09:00 MHDA- 2000/04/25 09:00 CRDT- 1999/12/22 09:00 PHST- 1999/12/22 09:00 [pubmed] PHST- 2000/04/25 09:00 [medline] PHST- 1999/12/22 09:00 [entrez] AID - 10.1084/jem.190.12.1793 [doi] PST - ppublish SO - J Exp Med. 1999 Dec 20;190(12):1793-800. doi: 10.1084/jem.190.12.1793.