T cell receptor expression can switch on and off at a posttranslational level.
The human T acute lymphocytic leukemia cell line, SUP-T13, is a mosaic of TCR/CD3+ and TCR/CD3- cells. Individual SUP-T13 cells can spontaneously switch on and off surface TCR/CD3 expression. This switching was demonstrated by culturing and analysis of single cell clones that were TCR/CD3+ or TCR/CD3-. The rate of switching is about 10(-2)/cell per generation in either direction. This is too high to be due to a spontaneous mutation event. Furthermore, switched cells can revert at similar rates, as demonstrated by repeated cloning and reanalysis. This makes it likely that a regulatory change is responsible for switching. In support of this, all known TCR/CD3 proteins are found intracellularly in TCR/CD3- cells, and they associate with each other as in TCR/CD3+ cells. Furthermore, no structural abnormalities of the TCR/CD3 chains can be seen in TCR/CD3- cells using two-dimensional electrophoresis. However, in these cells, the chains accumulate in great excess intracellularly. This accumulation is specific to the TCR/CD3 complex, as other glycoproteins are still expressed normally on the cell surface. Thus, there is regulation of TCR expression at a posttranslational level. These TCR/CD3- cells may lead to the identification of novel protein(s) involved in glycosylating, processing, or transporting the TCR/CD3 complex. Potential loss of TCR/CD3 expression may also limit the feasibility of TCR-based therapies for T cell leukemias.
Maecker
H T
HT
Department of Biology, Loyola University of Chicago, IL 60626.
Jokinen
D M
DM
Fisher
R I
RI
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D006801:Humans; D015458:Leukemia, T-Cell / Q000276:immunology*; D014176:Protein Biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell