The duration of TCR/pMHC interactions regulates CTL effector function and tumor-killing capacity

Riquelme E.; Carreno, LJ; Gonzalez PA; Kalergis, AM

Abstract

Effector CTL contribute to tumoral immunity by killing tumor cells through secretion of cytotoxic granules and cytokines. Activation of CTL requires specific recognition of cognate peptide-MHC-I (pMHC) complexes on the tumor cell surface by the CTL TCR. It has been suggested that the half-life (t 1/2) of the TCR/pMHC interaction modulates the activation of naïve CD8+ T cells; however, it remains unknown whether CTL effector function can also be regulated by the TCR/pMHC t1/2. Here, we have studied CTL activity in response to tumor cells loaded with pMHC that bind the TCR with different t1/2. We observed that the TCR/pMHC t1/2 can differentially regulate CTL effector function during the interaction with tumor cells and defines the nature of anti-tumoral CTL responses in vivo. Although prolonged TCR/pMHC t1/2 promoted only partial expression of cytotoxic molecules, short t1/2 induced partial polarization of lytic machinery toward target cells. In contrast, intermediate TCR/pMHC t1/2 induced strong expression of cytotoxic molecules, efficient polarization of lytic machinery and subsequent release of toxic granules by CTL that killed tumor cells. Consistently, efficient in vivo CTL-mediated tumor clearance was only observed for tumors expressing intermediate t1/2 pMHC ligands. These data suggest that there is an optimal TCR/pMHC t1/2 for efficient CTL activity. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

Más información

Título según WOS: The duration of TCR/pMHC interactions regulates CTL effector function and tumor-killing capacity
Título según SCOPUS: The duration of TCR/pMHC interactions regulates CTL effector function and tumor-killing capacity
Título de la Revista: EUROPEAN JOURNAL OF IMMUNOLOGY
Volumen: 39
Número: 8
Editorial: WILEY-BLACKWELL
Fecha de publicación: 2009
Página de inicio: 2259
Página final: 2269
Idioma: English
URL: http://doi.wiley.com/10.1002/eji.200939341
DOI:

10.1002/eji.200939341

Notas: ISI, SCOPUS