The Journal of Experimental Medicine · 1991 · 347 citations · 23 references
Life SciencesImmunologyMolecular BiologyImmunoregulationMolecular ImmunologySignal TransductionAntigen RecognitionB Cell ActivationCostimulatory SignalingLymphocyte ActivationT Cell ActivationT Cell BiologyAntigen Presenting Cell Costimulatory MoleculesB7 Family Immunoregulatory LigandsCd28 CostimulationCd28 SignalingCell Proliferation KineticsCostimulatory Signal TransductionInterferon Gamma ProductionMurine Models
T cell activation requires a second costimulatory signal from ligands on antigen‑presenting cells, such as the human B7 protein that engages CD28 on T cells. The murine B7 homolog was cloned, shares 44% identity with human B7, is expressed in B‑cell hematopoietic cells, and its transfected protein delivers costimulatory signals to human CD28+ T cells, indicating conserved ligand‑binding sites.
Following occupancy of the T cell receptor by antigen, T cell proliferation and lymphokine production are determined by a second costimulatory signal delivered by a ligand expressed on antigen presenting cells. The human B cell activation antigen B7, which is expressed on antigen presenting cells including activated B cells and gamma interferon treated monocytes, has been shown to deliver such a costimulatory signal upon attachment to its ligand on T cells, CD28. We have cloned and sequenced the murine homologue of the human B7 gene. The predicted murine protein has 44% amino acid identity with human B7. The greatest similarity is in the Ig-V and Ig-C like domains. Murine B7 mRNA was detected in murine hematopoietic cells of B cell but not T cell origin. Cells transfected with murine B7 provided a costimulatory signal to human CD28+ T lymphocytes. These results demonstrate the costimulatory activity of murine B7 and provide evidence that the ligand attachment site is conserved between the two species.
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A Cell Culture Model for T Lymphocyte Clonal Anergy
Ronald H. Schwartz · Science · 1990 · 1.9K citations