RESUMEN
Although presentation of antigen to the T cell receptor is necessary for the initiation of an immune response, additional molecules expressed on antigen-presenting cells deliver essential costimulatory signals. T cell activation, in the absence of costimulation, results in T cell anergy. The B7-1 protein is a costimulator molecule that regulates interleukin-2 (IL-2) secretion by signaling through the pathway that uses CD28 and CTLA-4 (hereafter referred to as the CD28 pathway). We have cloned a counter-receptor of CD28 and CTLA-4, termed B7-2. Although only 26 percent identical to B7-1, B7-2 also costimulates IL-2 production and T cell proliferation. Unlike B7-1, B7-2 messenger RNA is constitutively expressed in unstimulated B cells. It is likely that B7-2 provides a critical early costimulatory signal determining if the T cell will contribute to an immune response or become anergic.
Asunto(s)
Antígenos CD , Antígenos de Diferenciación/metabolismo , Linfocitos B/inmunología , Antígeno B7-1/inmunología , Clonación Molecular , Inmunoconjugados , Activación de Linfocitos , Glicoproteínas de Membrana , Linfocitos T/inmunología , Abatacept , Secuencia de Aminoácidos , Animales , Linfocitos B/metabolismo , Antígeno B7-1/química , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Antígeno B7-2 , Antígenos CD28/metabolismo , Antígeno CTLA-4 , Línea Celular , ADN Complementario/genética , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia , Transducción de SeñalRESUMEN
The regulation of T cell-mediated immune responses requires a balance between amplification and generation of effector function and subsequent selective termination by clonal deletion. Although apoptosis of previously activated T cells can be induced by signaling of the tumor necrosis factor receptor family, these molecules do not appear to regulate T-cell clonal deletion in an antigen-specific fashion. We demonstrate that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes. This function appears to be antigen-restricted, since a concomitant signal T-cell receptor signal is required. Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells.