PD-L1 interacts specifically with B7-1 to inhibit T cell proliferation
Pathways in the B7:CD28 family regulate T cell activation and tolerance. B7 dependent responses in CD28/CTLA-4-/- T cells together with reports of stimulatory and inhibitory functions for PD-L1 and PD-L2 have suggested additional receptors for these B7 family members. We show that B7-1 and PD-L1 interact with an affinity intermediate to that of B7-1:CD28 and B7-1:CTLA-4. The PD-L1:B7-1 interface overlaps with the B7-1:CTLA-4 and PD-L1:PD-1 interfaces. We show that the interaction of B7-1 with PD-L1 inhibits T cell activation and cytokine production by comparing responses of T cells deficient in the well-described (CD28, CTLA4, and PD-1) and newly-characterized (B7-1 and PD-L1) receptors to either B7-1-Ig or PD-L1-Ig. The responses of PD-1-/- vs. PD-1/B7-1-/- T cells to PD-L1 and CD28/CTLA-4-/- vs. CD28/CTLA-4/PD-L1-/- T cells to B7-1 demonstrate that PD-L1 and B7-1 interact specifically to inhibit T cell activation. Our findings point to a significant bidirectional inhibitory interaction between B7-1 and PD-L1 and add an additional dimension to immunoregulatory functions of the B7:CD28 family.
The authors disclose no financial conflicts of interest.
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