Limited Density of an Antigen Presented by RMA-S Cells Requires B7-1/CD28 Signaling to Enhance T-cell Immunity at the Effector Phase

Funding Source

National Institutes of Health, Louisiana Cancer Research Consortium, Dutch Cancer Society

Grant Number

8G12MD007595, UL2010-4785, P20GM103424


Department of Biology

Document Type


Publication Date



he association of B7-1/CD28 between antigen presenting cells (APCs) and T-cells provides a second signal to proliferate and activate T-cell immunity at the induction phase. Many reports indicate that tumor cells transfected with B7-1 induced augmented antitumor immunity at the induction phase by mimicking APC function; however, the function of B7-1 on antitumor immunity at the effector phase is unknown. Here, we report direct evidence of enhanced T-cell antitumor immunity at the effector phase by the B7-1 molecule. Our experiments in vivo and in vitro indicated that reactivity of antigen-specific monoclonal and polyclonal T-cell effectors against a Lass5 epitope presented by RMA-S cells is increased when the cells expressed B7-1. Use of either anti-B7-1 or anti-CD28 antibodies to block the B7-1/CD28 association reduced reactivity of the T effectors against B7-1 positive RMA-S cells. Transfection of Lass5 cDNA into or pulse of Lass5 peptide onto B7-1 positive RMA-S cells overcomes the requirement of the B7-1/CD28 signal for T effector response. To our knowledge, the data offers, for the first time, strong evidence that supports the requirement of B7-1/CD28 secondary signal at the effector phase of antitumor T-cell immunity being dependent on the density of an antigenic peptide.


DOI: 10.1371/journal.pone.0108192

PubMed ID: 25383875

Funding: This study was supported by funding from NIH (RCMI, 8G12MD007595), Louisiana Cancer Research Consortium (LCRC) and Xavier University’s Center for Undergraduate Research (CUR) to Dr. Qian-Jin Zhang. Dr. Thorbald van Hallwas supported by Dutch Cancer Society (UL2010-4785). Dr. Harris McFerrin was supported by funding from the NIGMS (P20GM103424). This study was also supported by funding from Louisiana Board of Regents Eminent Alumni Scholars Program, Kellogg Professorship IV in the Arts and Sciences to Dr. Shubha P. Kale. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.