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Semin Immunopathol. 2010 Jun;32(2):137-48. doi: 10.1007/s00281-010-0197-9. Epub 2010 Feb 21.

Cbl-b in T-cell activation.

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IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohrgasse 3, 1030, Vienna, Austria.


Peripheral activation of antigen-specific T cells is stringently controlled to prevent immune responses against self-antigens. Only after a T cell is presented with two signals, an antigen and a co-stimulatory signal, can they be fully activated. In case antigen presentation occurs without co-stimulation, T-cell receptor (TCR) signaling pathways are regulated to prevent T-cell activation and induce T-cell tolerance. Thus, for a productive T-cell response to occur, co-stimulatory receptors need to serve the dual role of amplifying the TCR signaling while concomitantly releasing T cells from suppression. Biochemical and genetic studies during the last 10 years have documented the critical role of the E3 ubiquitin-ligase Cbl-b in this fundamental two-signal modulation of T-cell responses. In this review, we will discuss our current understanding on how Cbl-b controls T-cell activation and tolerance, its in vivo implications, as well as mechanisms for tuning T-cell-mediated immune responses by this essential E3 ligase.

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