Limited density of an antigen presented by RMA-S cells requires B7-1/CD28 signaling to enhance T-cell immunity at the effector phase.
The 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.
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Xiao-Lin
XL
Li
Clinical Oncology, K1-P, Leiden University Medical Center, Leiden, the Netherlands.
Marjolein
M
Sluijter
Clinical Oncology, K1-P, Leiden University Medical Center, Leiden, the Netherlands.
Elien M
EM
Doorduijn
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Shubha P
SP
Kale
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Harris
H
McFerrin
Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, Monroe, Louisiana, United States of America.
Yong-Yu
YY
Liu
College of Chemistry & Environmental Science, Hebei University, Hebei Province, Baoding, China; Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Yan
Y
Li
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Madhusoodanan
M
Mottamal
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Xin
X
Yao
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Fengkun
F
Du
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Baihan
B
Gu
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Kim
K
Hoang
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Yen H
YH
Nguyen
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Nichelle
N
Taylor
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Chelsea R
CR
Stephens
Clinical Oncology, K1-P, Leiden University Medical Center, Leiden, the Netherlands.
Thorbald
T
van Hall
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
Qian-Jin
QJ
Zhang
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D008565:Membrane Proteins; C479747:Trh4 protein, mouse