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Elsevier, Immunity, 1(35), p. 97-108, 2011

DOI: 10.1016/j.immuni.2011.04.020



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The Costimulatory Molecule CD27 Maintains Clonally Diverse CD8+ T Cell Responses of Low Antigen Affinity to Protect against Viral Variants

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.