B7-1-HSA (CD80-CD24), a recombinant hybrid costimulatory molecule retains ligand binding and costimulatory functions.
Optimal activation of naïve T lymphocyte requires two signals; an antigen-specific signal initiated by engagement of TCR with the antigen-MHC complex and a costimulatory signal independent of the antigen receptor complex. Without the costimulatory signal, T cells become anergic. Various adhesion molecules, such as B7-1 (CD80) and heat stable antigen (HSA, CD24), expressed on antigen presenting cells have been demonstrated to provide costimulatory signals to T cells. It was reported that the combinations of different adhesion molecules could induce even stronger immune response. In this study, we made a hybrid costimulatory molecule, B7-1-HSA, and tested its T cell stimulatory function. Chinese hamster ovary (CHO) cells expressing this hybrid molecule bound both anti-CD80 and anti-CD24 monoclonal antibodies, and induced stronger T cell proliferation than CHO cells expressing B7-1 or HSA alone. These results suggest that the B7-1-HSA hybrid molecule can deliver two costimulatory signals simultaneously that can synergize in inducing T cell proliferation. The purified B7-1-HSA protein reacted with both anti-B7-1 and anti-HSA mAbs in Western blotting and specifically mediated adhesion of Jurkat cells. Furthermore, purified B7-1-HSA molecule spontaneously incorporated onto cell membrane through its glycolipid anchor suggesting that this hybrid costimulatory molecule can be used in protein transfer to develop effective cancer vaccines.
Wang
Yi-Chong
YC
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Sashidharamurthy
Rangaiah
R
Nagarajan
Shanmugam
S
Selvaraj
Periasamy
P
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051927:CD24 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D015870:Gene Expression; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D008024:Ligands; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014162:Transfection
D018122:B7-1 Antigen; D051927:CD24 Antigen; D018076:DNA, Complementary; D000939:Epitopes; D017261:Glycosylphosphatidylinositols; D008024:Ligands; D011993:Recombinant Fusion Proteins