Human T cell leukemia virus type I prevents cell surface expression of the T cell receptor through down-regulation of the CD3-gamma, -delta, -epsilon, and -zeta genes.
Infection and transformation by human T cell leukemia virus type I (HTLV-I) up-regulates expression of several inducible genes including those coding for cytokines involved in the proliferation of normal and leukemic T cells. We demonstrate that HTLV-I can also shut off expression of the CD3-gamma, delta, epsilon, and zeta genes that code for the constant elements of the TCR for Ag. In addition, the T cell-specific CD3-epsilon enhancer was found to be inactive in a HTLV-I-infected T cell clone. This HTLV-I-infected T cell clone (827-p19-II) that could be cultured in the absence of IL-2 lacked the CD3 proteins but did express the TCR-alpha and -beta proteins intracellularly. In the absence of the CD3-gamma, delta, epsilon, and zeta polypeptide chains the disulfide bridged TCR-alpha/beta heterodimer was not formed and the Ag receptor did not appear at the cell surface. These results allowed two major conclusions: first, HTLV-I infection has an effect on the T cell specific regulatory elements that coordinately regulate CD3-gamma, delta, epsilon, and zeta expression and second, the CD3-gamma, delta, epsilon, and zeta proteins are necessary for formation and routing the variable TCR-alpha/beta (or -gamma/delta) heterodimer to the human T cell surface.
de Waal Malefyt
R
R
DNAX Research Institute, Department of Human Immunology, Palo Alto CA 94304-1104.
Yssel
H
H
Spits
H
H
de Vries
J E
JE
Sancho
J
J
Terhorst
C
C
Alarcon
B
B
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D015152:Blotting, Northern; D015139:Blotting, Southern; D017252:CD3 Complex; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D015490:HTLV-I Infections / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell