The CD8(+) T cell response to Moloney-murine leukemia virus (M-MuLV)-induced Ags is almost entirely dominated by the exclusive expansion of lymphocytes that use preferential TCRVbeta chain rearrangements. In mice lacking T cells expressing these TCRVbeta, we demonstrate that alternative TCRVbeta can substitute for the lack of the dominant TCRVbeta in the H-2-restricted M-MuLV Ag recognition. We show that, at least for the H-2(b)-restricted response, the shift of TCR usage is not related to a variation of the immunodominant M-MuLV epitope recognition. After virus immunization, all the potentially M-MuLV-reactive lymphocytes are primed, but only the deletion of dominant Vbeta rescues the alternative Vbeta response. The mechanism of clonal T cell "immunodomination" that guides the preferential Vbeta expansion is likely the result of a proliferative advantage of T cells expressing dominant Vbeta, due to differences in TCR affinity and/or cosignal requirements. In this regard, a CD8 involvement is strictly required for the virus-specific cytotoxic activity of CTL expressing alternative, but not dominant, Vbeta gene rearrangements. The ability of T cells expressing alternative TCRVbeta rearrangements to mediate tumor protection was evaluated by a challenge with M-MuLV tumor cells. Although T cells expressing alternative Vbeta chains were activated and expanded, they were not able to control tumor growth in a long-lasting manner due to their incapacity of conversion and accumulation in the T central memory pool.

A large number of T lymphocytes recognize Moloney-murine leukemia virus-induced antigens, but a few mediate long-lasting tumor immunosurveillance

ROSATO, ANTONIO;
2005

Abstract

The CD8(+) T cell response to Moloney-murine leukemia virus (M-MuLV)-induced Ags is almost entirely dominated by the exclusive expansion of lymphocytes that use preferential TCRVbeta chain rearrangements. In mice lacking T cells expressing these TCRVbeta, we demonstrate that alternative TCRVbeta can substitute for the lack of the dominant TCRVbeta in the H-2-restricted M-MuLV Ag recognition. We show that, at least for the H-2(b)-restricted response, the shift of TCR usage is not related to a variation of the immunodominant M-MuLV epitope recognition. After virus immunization, all the potentially M-MuLV-reactive lymphocytes are primed, but only the deletion of dominant Vbeta rescues the alternative Vbeta response. The mechanism of clonal T cell "immunodomination" that guides the preferential Vbeta expansion is likely the result of a proliferative advantage of T cells expressing dominant Vbeta, due to differences in TCR affinity and/or cosignal requirements. In this regard, a CD8 involvement is strictly required for the virus-specific cytotoxic activity of CTL expressing alternative, but not dominant, Vbeta gene rearrangements. The ability of T cells expressing alternative TCRVbeta rearrangements to mediate tumor protection was evaluated by a challenge with M-MuLV tumor cells. Although T cells expressing alternative Vbeta chains were activated and expanded, they were not able to control tumor growth in a long-lasting manner due to their incapacity of conversion and accumulation in the T central memory pool.
File in questo prodotto:
File Dimensione Formato  
Lavoro 41.pdf

non disponibili

Tipologia: Published (publisher's version)
Licenza: Accesso privato - non pubblico
Dimensione 250.46 kB
Formato Adobe PDF
250.46 kB Adobe PDF Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/1482362
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 9
social impact