title: Interaction of human PD-L1 and B7-1.
abstract: Numerous studies have pointed to the role of programmed death-1 ligand 1 (PD-L1) in regulating tolerance, chronic infection, and tumor immunity. Recently, we have identified murine B7-1 as a new binding partner for murine PD-L1. Human and mouse B7-1 share only 46% identity, leading us to question whether human B7-1 and PD-L1 can participate in a similar interaction. Here we show that human B7-1 can interact with human PD-L1 with affinity greater than that of B7-1 with CD28, but less than that of B7-1 with CTLA-4 or of PD-L1 with PD-1. We characterize a series of anti-human PD-L1 monoclonal antibodies and identify antibodies that can block interactions of PD-L1 with B7-1, PD-1, or both. Since PD-L1 and CD28 on T cells may compete for B7-1 as a binding partner and CD8 T cells may express high or low levels of CD28, we examined when PD-L1 and CD28 are co-expressed on CD8 T cells. We compared the time-course and extent of PD-L1 induction on CD8 CD28high versus CD28low T cells following stimulation with anti-CD3. We show that PD-L1 is induced to a higher level on CD28high T cells than on CD28low T cells upon activation. These results suggest that PD-L1 may play an important and undervalued role on human T cells.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Manish J
authors.initials: MJ
authors.lastname: Butte
authors.forename: Victor
authors.initials: V
authors.lastname: Peña-Cruz
authors.forename: Mi-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen; D018106:CD28 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D011485:Protein Binding; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018106:CD28 Antigens