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. 2022 Mar 21;13:827921. doi: 10.3389/fimmu.2022.827921

Figure 1.

Figure 1

Mechanisms responsible for the generation of soluble PD-1 and PD-L1. (A) Generation of soluble PD-1 from splice variants of PD-1 mRNA. Full length PD-1 (flPD-1) mRNA contains five exons (exons 1–5), which encode a short signal sequence, an immunoglobulin (Ig) domain, the stalk and transmembrane (TM) domain, a 12 amino acid (aa) sequence that marks the beginning of the cytoplasmic domain, the C-terminal intracellular (IC) domain and a long 3’UTR, respectively. Four splice variants of PD-1 mRNA, PD-1Deltaex2, PD-1Deltaex3, PD-1Deltaex2/3, and PD-1Deltaex2/3/4, have been cloned from human peripheral blood mononuclear cells (PBMCs). PD-1Deltaex3 only lacks exon 3, but retains an extracellular Ig domain. Translation of this mRNA results in a soluble form PD-1. (B) Generation of soluble PD-L1 by proteolytic cleavage of membrane-bound PD-L1. Several proteases, including MMPs and ADAMs, are capable of cleaving membrane-bound PD-L1, releasing soluble PD-L1.