Cloning and Characterization of Porcine 4Ig-B7-H3: A Potent Inhibitor of Porcine T-Cell Activation

BACKGROUND: Members of the B7 superfamily costimulate the proliferation of lymphocytes during the initiation and maintenance of antigen-specific humoral and cell-mediated immune responses. B7-H3 (CD276) is a newly identified member of the B7 superfamily. It has been shown that B7-H3 plays a significant role in regulating T cell response in humans and mice, but it is not known whether a counterpart of human or murine B7-H3 exists in porcine species. METHODOLOGY/PRINCIPAL FINDINGS: We cloned the porcine 4ig-b7-h3 gene using a blast search at the NCBI database with human b7-h3, RT-PCR and 3'-terminus RACE. Protein sequence analysis showed that the protein encoded by this gene contained 4Ig-like domains and was 90.88% identical with human 4Ig-B7-H3. Results of Dot-blot hybridization and RT-PCR showed that B7-H3 was broadly distributed in porcine tissues mainly as two isoforms, 2Ig-B7-H3 and 4Ig-B7-H3, of which 4Ig-B7-H3 was dominant. We further demonstrated that porcine 4Ig-B7-H3 was able to inhibit the proliferation and cytokine production of porcine T cells activated through the TCR pathway, similar to human B7-H3. CONCLUSION: We cloned the porcine 4ig-b7-h3 gene and demonstrated that the porcine 4Ig-B7-H3 serves as a negative regulator for the T-cell immune response.