Altered thymic positive selection and intracellular signals in Cbl-deficient mice

Mayumi Naramura, Hemanta K. Kole, Ren Ju Hu, Hua Gu

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Abstract

Cbl is the product of the protooncogene c-cbl and is involved in T cell antigen receptor (TCR)-mediated signaling. To understand the role of Cbl for immune system development and function, we generated a Cbl-deficient mouse strain. In Cbl-deficient mice, positive selection of the thymocytes expressing major histocompatibility complex class II-restricted transgenic TCR was significantly enhanced. Two factors may have contributed to the altered thymic selection. First, Cbl deficiency markedly up-regulated the activity of ZAP-70 and mitogen-activated protein kinases. The mitogen-activated protein kinase pathway was shown previously to be involved in thymic positive selection. Second, Cbl-deficient thymocytes expressed CD3 and CD4 molecules at higher levels, which consequently may increase the avidity of TCR/ major histocompatibility complex/coreceptor interaction. Thus, Cbl plays a novel role in modulating TCR-mediated multiple signaling pathways and fine-tunes the signaling threshold for thymic selection.

Original languageEnglish (US)
Pages (from-to)15547-15552
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number26
DOIs
StatePublished - Dec 22 1998

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