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. Author manuscript; available in PMC: 2019 Sep 20.
Published in final edited form as: Receptors Clin Investig. 2017 Sep 25;4:e1581.

Figure 1. CD28 family of receptors and an interplay between PD-1 and CD28. Upper:

Figure 1.

Diagram showing the structure of the antigen-receptor (TCR) and co-receptors CD28, ICOS, PD-1 and CTLA-4 on T-cells. CD4/CD8-p56lck phosphorylates the TCR leading to the recruitment of ZAP-70. CD28 and ICOS send positive signals while PD-1 and CTLA-4 dampen the immune response. Lower: Illustration showing the interplay between PD-1 and CD28 at the level of signaling. p56lck phosphorylates tyrosine residues on PD-1 and CD28 which allows CD28 to recruit PI 3K and GRB2, whereas PD-1 recruits the phosphatases SHP-2 (Shp2) and SHP-1 (Shp1). PI 3K binds to the CD28 pYMNM motif, while the SHP-2 (Shp2) binds to the ITIM and ITSM tyrosine motifs in PD-1. SHP2 showed a marked preference in dephosphorylating CD28 (including the pYMNM motif) relative to other substrates such as the TCRzeta chain and the co-receptor ICOS.