Cytoplasmic tail deletion of T cell receptor (TCR) beta-chain results in its surface expression as glycosylphosphatidylinositol-anchored polypeptide on mature T cells in the absence of TCR-alpha.
Surface expression of the T cell antigen receptor (TCR) in mature T cells requires the association of a variable heterodimer (alpha.beta or gamma.delta) with six invariant CD3 polypeptides (gamma, delta, epsilon-epsilon, zeta-zeta, or zeta-eta). We described here that deletion of the cytoplasmic tail polypeptide sequence (Lys-Lys-Lys-Asn-Ser) of TCR beta-chain (beta CT) results in expression of the truncated beta-chain on the surface of a mature T cell hybridoma line, in the absence of TCR-alpha, as a glycophosphatidylinositol (GPI)-anchored monomeric polypeptide. The GPI-anchored TCR-beta CT is not associated with CD3-epsilon and is incapable of conventional signal transduction. Association with TCR-alpha prevents beta CT from GPI-linkage formation. The alpha beta CT heterodimer binds the CD3 polypeptides, and the resultant TCR alpha beta CT/CD3 complex is capable of signal transduction. Our data show that a signal sequence for GPI-linkage formation is present in TCR-beta, and this alternative membrane anchoring mechanism can be utilized by beta-chain polypeptide lacking the CT sequence. We conclude therefore that in the absence of TCR-alpha expression, the beta-chain CT sequence plays an essential function in hindering GPI-linkage formation, thereby preventing escape of incompletely assembled TCR beta-chain to the cell surface of mature T cells.
Bell
L M
LM
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Solomon
K R
KR
Gold
J P
JP
Tan
K N
KN
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D017384:Sequence Deletion; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D018076:DNA, Complementary; D017261:Glycosylphosphatidylinositols; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase