TCR ζ-chain downregulation: Curtailing an excessive inflammatory immune response

Michal Baniyash*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

303 Scopus citations


The T-cell receptor (TCR) functions in both antigen recognition and signal transduction, which are crucial initial steps of antigen-specific immune responses. TCR integrity is vital for the induction of optimal and efficient immune responses, including the routine elimination of invading pathogens and the elimination of modified cells and molecules. Of the TCR subunits, the ζ-chain has a key role in receptor assembly, expression and signalling. Downregulation of TCR ζ-chain expression and impairment of T-cell function have been shown for T cells isolated from hosts with various chronic pathologies, including cancer, and autoimmune and infectious diseases. This review summarizes studies of the various pathologies that show this phenomenon and provides new insights into the mechanism responsible for downregulation of ζ-chain expression, its relevance and its clinical implications.

Original languageAmerican English
Pages (from-to)675-687
Number of pages13
JournalNature Reviews Immunology
Issue number9
StatePublished - Sep 2004

Bibliographical note

Funding Information:
I gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center, New York, United States, the Concern Foundation of Los Angeles, United States, and the Harold B. Abramson Chair in Immunology, Jerusalem, Israel. This study was supported by The Israel Academy of Sciences and Humanities, and by The Joseph and Matilda Melnick fund Houston, United States.


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