The Costimulatory Molecule CD27 Maintains Clonally Diverse CD8+ T Cell Responses of Low Antigen Affinity to Protect against Viral Variants.
van Gisbergen, Klaas P.J.M. 1,3,*; Klarenbeek, Paul L. 2; Kragten, Natasja A.M. 1,3; Unger, Peter-Paul A. 1; Nieuwenhuis, Marieke B.B. 1; Wensveen, Felix M. 1; ten Brinke, Anja 4; Tak, Paul P. 2; Eldering, Eric 1; Nolte, Martijn A. 1,3; van Lier, Rene A.W. 1,3
[Article] Immunity. 35(1):97-108, July 2011.

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SUMMARY: 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.

(C) 2011Elsevier, Inc.