Dissection of the role of CD3gamma chains in profound but reversible T-cell receptor down-regulation.
T-lymphocyte activity in the immune system is regulated by the quantity of surface membrane T-cell antigen receptors (TCR). The amount of surface-bound TCR is dependent on the rate of [1] biosynthesis, assembly and intracellular transport of the individual chains composing the TCR/CD3 complex and [2] the internalization and recycling of the receptors. The TCR-ligand interaction augments receptor internalization. In the present paper, we have studied short- and long-term down-regulation of TCR/CD3 complexes with monoclonal anti-TCR/CD3 antibodies, and attempted to determine which component(s) of the TCR/CD3 complex are responsible for these two phenomena. Our data indicate that short- and long-term down-regulation is mediated by different mechanisms, and that the extracellular and/or transmembrane regions of CD3gamma molecules appear to play an important role in chronic TCR/CD3 down-regulation and subsequent deficient re-expression. These results may have important implications for the understanding of induction of T-cell tolerance or anergy.
Unité de Physiopathologie Cellulaire et moléculaire, CNRS UPR 2163, Institut Claude de Preval, IFR 30, CHU de PURPAN, 31059 Toulouse Cedex 03, France.
B
B
Rubin
R
R
Llobera
C
C
Gouaillard
A
A
Alcover
J
J
Arnaud
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D019169:Jurkat Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C115335:CD3E protein, human; D018076:DNA, Complementary; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell