Controlling PD-L1 in cis

Science (2019)

The co-inhibitory receptor PD-1 is important for restraining T cell responses; however, as it is rapidly upregulated on T cells (hours after activation), it is unclear how its effects are curtailed to allow a productive response. In Science, Okazaki and colleagues find that the PD-1 ligand PD-L1 and the co-stimulatory molecule CD80 interact in cis on the surface of antigen-presenting cells. This cis interaction prevents PD-L1 from binding to its receptor PD-1 on T cells and therefore mitigates its inhibitory effects. Interestingly, the functionally closely related molecule CD86 does not demonstrate this interaction with PD-L1. Mutations in the gene encoding PD-L1 or CD80 that prevent their interaction dampen T cell activation both in vitro and in vivo in the context of cancer and autoimmune responses.

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Correspondence to Zoltan Fehervari.

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Fehervari, Z. Controlling PD-L1 in cis. Nat Immunol 20, 665 (2019).

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