Biochemical and Biophysical Research Communications
Differential binding properties of B7-H1 and B7-DC to programmed death-1☆
Section snippets
Materials and methods
Constructs. Human PD-1 cDNA was generated by RT-PCR from peripheral blood mononuclear cells using primers shown in Table 1 and subsequently subcloned into a pMKITneo vector, kindly provided by K. Maruyama (Tokyo Medical and Dental University, Tokyo). Constructs for Ig fusion proteins consisting of the extracellular portion of human PD-1, B7-H1, or B7-DC and the hinge-CH2-CH3 domains of human IgG1 heavy chain were prepared as described previously [28]. The extracellular portions of each molecule
Characterization of B7-H1Ig, B7-DCIg, and PD-1Ig fusion proteins
To characterize the interactions of B7-H1 and B7-DC with PD-1, we generated soluble fusion proteins consisting of the extracellular region of these molecules and the Fc portion of human IgG1. As shown in Fig. 1, SDS–PAGE analysis showed a single band of 150–170 kDa for B7-H1Ig, B7-DCIg, and PD-1Ig under non-reducing conditions, and each band migrated at approximately half size under reducing conditions. These results indicated homo-dimerization of these Ig fusion proteins by disulfide-linkage,
Discussion
Here, we demonstrated that the relative affinity of PD-1 to B7-DC was 2–6-fold higher than that to B7-H1 as estimated by flow cytometric and SPR analyses. The differences in Kd values obtained by flow cytometry and SPR may result from structural differences between the cell surface molecules on transfectants and the immobilized dimeric forms of Ig fusion proteins on BIAcore sensor. However, a higher affinity of B7-DC/PD-1 interaction than B7-H1/PD-1 interaction was consistently observed in both
Acknowledgements
This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology, and from the Ministry of Health, Labor, and Welfare of Japan.
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Abbreviations: PD-1, programmed death-1; SPR, surface plasmon resonance; MFI, mean fluorescence intensity; RU, response unit; kon, association rate constant; koff, dissociation rate constant; Rmax, maximum response.