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

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

Research output: Contribution to journalArticle

273 Citations (Scopus)

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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T-Cell Antigen Receptor
Thymocytes
Mitogen-Activated Protein Kinases
Major Histocompatibility Complex
CD4 Antigens
Immune System

ASJC Scopus subject areas

  • General

Cite this

Altered thymic positive selection and intracellular signals in Cbl-deficient mice. / Naramura, Mayumi; Kole, Hemanta K.; Hu, Ren Ju; Gu, Hua.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 26, 22.12.1998, p. 15547-15552.

Research output: Contribution to journalArticle

Naramura, Mayumi ; Kole, Hemanta K. ; Hu, Ren Ju ; Gu, Hua. / Altered thymic positive selection and intracellular signals in Cbl-deficient mice. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 26. pp. 15547-15552.
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