Ligand-induced TCR down-regulation is not dependent on constitutive TCR cycling.
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.
Dietrich
Jes
J
Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.
Menné
Charlotte
C
Lauritsen
Jens Peter H
JP
von Essen
Marina
M
Rasmussen
Anette B
AB
Ødum
Niels
N
Geisler
Carsten
C
D020816:Amino Acid Motifs; D017252:CD3 Complex / Q000502:physiology; D015536:Down-Regulation; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D011493:Protein Kinase C / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*
D017252:CD3 Complex; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D011493:Protein Kinase C