Distinct and non-overlapping t cell receptor repertoires expanded by dna vaccination in wild-type and her-2 transgenic balb/c mice.

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.

@Article{SCSOGFF06a,
  author       = {Simona, R. and Chiara, N. and Silvia, M. and Orsini, M. and Guido, F. and Federica, C. and Francesco, R.},
  title        = {Distinct and non-overlapping t cell receptor repertoires expanded by dna vaccination in wild-type and her-2 transgenic balb/c mice.},
  journal      = {J Immunol},
  number       = {11},
  volume       = {177},
  pages        = {7626--7633},
  year         = {2006},
  note         = {issn: 0022-1767 (Print)
language: eng
idxproject: ?

address: Dipartimento di Scienze Cliniche e Biologiche, University of Turin, Turin, Italy.},
  keywords     = {Bioinformatics; Amino Acid Sequence; Animals; Antigens, Neoplasm/immunology; CD4-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/immunology; Female; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Genes, T-Cell Receptor beta; *Immune},
  url          = {https://publications.crs4.it/pubdocs/2006/SCSOGFF06a},
}