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Immunity. 2011 Jul 22;35(1):97-108. doi: 10.1016/j.immuni.2011.04.020. Epub 2011 Jul 14.

The costimulatory molecule CD27 maintains clonally diverse CD8(+) T cell responses of low antigen affinity to protect against viral variants.

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Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.


CD70 and CD27 are costimulatory molecules that provide essential signals for the expansion and differentiation of CD8(+) T cells. Here, we show that CD27-driven costimulation lowered the threshold of T cell receptor activation on CD8(+) T cells and enabled responses against low-affinity antigens. Using influenza infection to study in vivo consequences, we found that CD27-driven costimulation promoted a CD8(+) T cell response of overall low affinity. These qualitative effects of CD27 on T cell responses were maintained into the memory phase. On a clonal level, CD27-driven costimulation established a higher degree of variety in memory CD8(+) T cells. The benefit became apparent when mice were reinfected, given that CD27 improved CD8(+) T cell responses against reinfection with viral variants, but not with identical virus. We propose that CD27-driven costimulation is a strategy to generate memory clones that have potential reactivity to a wide array of mutable pathogens.

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