Ligand-induced TCR down-regulation is not dependent on constitutive TCR cycling

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TCR internalization takes place both in resting T cells as part of constitutive TCR cycling, after PKC activation, and during TCR triggering. It is still a matter of debate whether these pathways represent distinct pathways. Thus, some studies have indicated that ligand-induced TCR internalization is regulated by mechanisms distinct from those involved in constitutive internalization, whereas other studies have suggested that the ligand-induced TCR internalization pathway is identical with the constitutive pathway. To resolve this question, we first identified requirements for constitutive TCR cycling. We found that in contrast to PKC-induced TCR internalization where both CD3gamma-S(126) and the CD3gamma leucine-based internalization motif are required, constitutive TCR cycling required neither PKC nor CD3gamma-S(126) but only the CD3gamma leucine-based motif. Having identified these requirements, we next studied ligand-induced internalization in cells with abolished constitutive TCR cycling. We found that ligand-induced TCR internalization was not dependent on constitutive TCR internalization. Likewise, constitutive internalization and recycling of the TCR were independent of an intact ligand-induced internalization of the TCR. In conclusion, ligand-induced TCR internalization and constitutive cycling of the TCR represents two independent pathways regulated by different mechanisms.
Original languageEnglish
JournalJournal of Immunology
Issue number11
Pages (from-to)5434-40
Number of pages6
Publication statusPublished - 2002

Bibliographical note

Keywords: Amino Acid Motifs; Antigens, CD3; Down-Regulation; Humans; Jurkat Cells; Ligands; Protein Kinase C; Receptors, Antigen, T-Cell

ID: 8544550