title: The costimulatory molecule CD27 maintains clonally diverse CD8(+) T cell responses of low antigen affinity to protect against viral variants.
abstract: 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.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. k.vangisbergen@sanquin.nl
authors.forename: Klaas P J M
authors.initials: KP
authors.lastname: van Gisbergen
authors.forename: Paul L
authors.initials: PL
authors.lastname: Klarenbeek
authors.forename: Natasja A M
authors.initials: NA
authors.lastname: Kragten
authors.forename: Peter-Paul A
authors.initials: PP
authors.lastname: Unger
authors.forename: Marieke B B
authors.initials: MB
authors.lastname: Nieuwenhuis
authors.forename: Felix M
authors.initials: FM
authors.lastname: Wensveen
authors.forename: Anja
authors.initials: A
authors.lastname: ten Brinke
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Eric
authors.initials: E
authors.lastname: Eldering
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Nolte
authors.forename: Rene A W
authors.initials: RA
authors.lastname: van Lier
mesh_terms: D000818:Animals; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002999:Clone Cells; D006801:Humans; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000956:Antigens, Viral; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7