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Distinct and non-overlapping T cell receptor repertoires expanded by DNA vaccination in wild-type and HER-2 transgenic BALB/c mice.
Rolla, Simona; Nicoló, Chiara; Malinarich, Silvia; Orsini, Massimiliano; Forni, Guido; Cavallo, Federica; Ria, Francesco.
Afiliación
  • Rolla S; Dipartimento di Scienze Cliniche e Biologiche, University of Turin, Turin, Italy.
J Immunol ; 177(11): 7626-33, 2006 Dec 01.
Article en En | MEDLINE | ID: mdl-17114432
ABSTRACT
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.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Receptor ErbB-2 / Escape del Tumor / Vacunas de ADN / Tolerancia Inmunológica Límite: Animals Idioma: En Revista: J Immunol Año: 2006 Tipo del documento: Article País de afiliación: Italia
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Receptor ErbB-2 / Escape del Tumor / Vacunas de ADN / Tolerancia Inmunológica Límite: Animals Idioma: En Revista: J Immunol Año: 2006 Tipo del documento: Article País de afiliación: Italia