Limited Density of an Antigen Presented by RMA-S Cells Requires B7-1/CD28 Signaling to Enhance T-cell Immunity at the Effector Phase
National Institutes of Health, Louisiana Cancer Research Consortium, Dutch Cancer Society
8G12MD007595, UL2010-4785, P20GM103424
Department of Biology
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.
Li, X.; Sluijter, M.; Doorduijn, E. M.; Ireland, Shubha Kale; McFerrin, H.; Ci, Y. Y.; Mottamal, M; Yao, X.; Du, F.; Gu, B.; Huang, K.; Nguyen, Y. H.; Taylor, N.; Stephens, C. R.; Van-Hall, T.; and Zhang, Qian-Jin, "Limited Density of an Antigen Presented by RMA-S Cells Requires B7-1/CD28 Signaling to Enhance T-cell Immunity at the Effector Phase" (2014). Faculty and Staff Publications. 174.