PMID- 17114432 OWN - NLM STAT- MEDLINE DCOM- 20070116 LR - 20210103 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 177 IP - 11 DP - 2006 Dec 1 TI - Distinct and non-overlapping T cell receptor repertoires expanded by DNA vaccination in wild-type and HER-2 transgenic BALB/c mice. PG - 7626-33 AB - Central tolerance to tumor-associated Ags is an immune-escape mechanism that significantly limits the TCR repertoires available for tumor eradication. The repertoires expanded in wild-type BALB/c and rat-HER-2/neu (rHER-2) transgenic BALB-neuT mice following DNA immunization against rHER-2 were compared by spectratyping the variable (V)beta and the joining (J)beta CDR 3. Following immunization, BALB/c mice raised a strong response. Every mouse used one or more CD8+ T cell rearrangements of the Vbeta9-Jbeta1.2 segments characterized by distinct length of the CDR3 and specific for 63-71 or 1206-1214 rHER-2 peptides. In addition, two CD4+ T cell rearrangements recurred in >50% of mice. Instead, BALB-neuT mice displayed a limited response to rHER-2. Their repertoire is smaller and uses different rearrangements confined to CD4+ T cells. Thus, central tolerance in BALB-neuT mice acts by silencing the BALB/c mice self-reactive repertoire and reducing the size of the CD8+ T cell component. CD8+ and CD4+ T cells from both wild-type and transgenic mice home to tumors. This definition of the T cell repertoires available is critical to the designing of immunological maneuvers able to elicit an effective immune reaction against HER-2-driven carcinogenesis. FAU - Rolla, Simona AU - Rolla S AD - Dipartimento di Scienze Cliniche e Biologiche, University of Turin, Turin, Italy. FAU - Nicolo, Chiara AU - Nicolo C FAU - Malinarich, Silvia AU - Malinarich S FAU - Orsini, Massimiliano AU - Orsini M FAU - Forni, Guido AU - Forni G FAU - Cavallo, Federica AU - Cavallo F FAU - Ria, Francesco AU - Ria F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, Neoplasm) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (Recombinant Proteins) RN - 0 (Vaccines, DNA) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antigens, Neoplasm/immunology MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Female MH - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor MH - Genes, T-Cell Receptor beta MH - *Immune Tolerance MH - Mice MH - Mice, Inbred BALB C MH - Mice, Transgenic MH - RNA, Messenger/analysis MH - Receptor, ErbB-2/*immunology MH - Receptors, Antigen, T-Cell/*immunology MH - Recombinant Proteins/immunology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transfection MH - *Tumor Escape MH - *Vaccines, DNA EDAT- 2006/11/23 09:00 MHDA- 2007/01/17 09:00 CRDT- 2006/11/23 09:00 PHST- 2006/11/23 09:00 [pubmed] PHST- 2007/01/17 09:00 [medline] PHST- 2006/11/23 09:00 [entrez] AID - 177/11/7626 [pii] AID - 10.4049/jimmunol.177.11.7626 [doi] PST - ppublish SO - J Immunol. 2006 Dec 1;177(11):7626-33. doi: 10.4049/jimmunol.177.11.7626.