Defective interactions between TCR chains and CD3 heterodimers prevent membrane expression of TCR-alpha beta in human T cells.
The human TCR complex is composed of two clonotypic polypeptide chains, TCR-alpha and TCR-beta (or TCR-gamma and TCR-delta) associated with CD3 gamma-, delta-, and epsilon-chains and zeta 2 homodimers. All six polypeptide chains are indispensable for TCR membrane expression and signaling function. In the present paper is described the analysis of a new TCR membrane-negative Jurkat T cell variant: E6.R3. The defect in this variant bears on the interaction between TCR and CD3 chains. E6.R3 cells have deleted three nucleotides in the TCR-alpha transmembrane (TM) region, which consequently lacks a leucine. This defect causes 1) lack of association between TCR alpha-chains and CD delta epsilon heterodimers; 2) lack of formation of disulphide-linked, fully glycosylated TCR-alpha beta heterodimers; and 3) lack of interaction between TCR-alpha beta/CD3 complexes and zeta-chains. Despite these defective interactions, TCR alpha-chains appear to become fully glycosylated, i.e., they are not retained in the endoplasmic reticulum but are further processed in the Golgi apparatus without such interactions. The defect may be due to the observation that in the E6.R3 TCR alpha- chains TM region, the two charged amino acids are situated on the same side of the alpha-helix; these two amino acids are exposed on opposite faces of the TM alpha-helix in normal TCR alpha-chains, possibly allowing TCR alpha-chains to interact with both CD3 delta- and CD3 epsilon-chains. Further possible consequences of the leucine deletion in the E6.R3 TCR-alpha TM region are discussed.
Arnaud
J
J
Laboratoire d'Immunologie Cellulaire et Molećulaire, CIGH/CNRS UPR 8291, Toulouse, France.
Chenu
C
C
Huchenq
A
A
Gouaillard
C
C
Kuhlmann
J
J
Rubin
B
B
D000595:Amino Acid Sequence; D001483:Base Sequence; D017252:CD3 Complex / Q000737:chemistry* / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta