The biosynthesis and assembly of T cell receptor alpha- and beta-chains with the CD3 complex.
The biosynthesis, processing, and assembly of the TCR alpha- and beta-chains with each other and with the CD3 complex were investigated on both cell surface positive (TCR+CD3-) and negative (TCR-CD3-) cell lines. The results indicate that 1) in cell surface TCR-CD3- cell lines (MOLT 3, CCRF-CEM), TCR-beta, but not alpha-chains are present intracellularly. TCR-beta-CD3 complexes are readily found in these cell lines, but no evidence for final processing or cell surface expression of such incomplete TCR-CD3 complexes is observed. 2) In the cell surface TCR+CD3+ cell line HPB-ALL, both alpha- and beta-chains are present intracellularly. Whereas non-glycosylated forms of TCR-beta chain can be detected, only more mature forms of TCR alpha-chains are detected indicating that the alpha-chains are more rapidly glycosylated than the beta-chains. 3) The large majority of the intracellular alpha- and beta-chains is not disulfide linked and a small fraction of these is associated with CD3. 4) Only small amounts of the total intracellular TCR chains are found as CD3-associated disulfide-linked alpha beta-heterodimers. 5) Final processing of TCR chains for cell surface expression takes place after formation of these TCR-alpha beta-CD3 complexes. Thus, both the TCR alpha- and beta-chains are over-produced and only relatively small amounts of these chains form CD3-associated heterodimers that are processed for cell surface expression. Analogous results were obtained with a non-leukemic CTL clone. Based on these observations, a model for the biosynthesis and assembly of the TCR-CD3 complex is presented.
Koning
F
F
Biological Resources Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Lew
A M
AM
Maloy
W L
WL
Valas
R
R
Coligan
J E
JE
D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D017252:CD3 Complex; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004220:Disulfides; D006031:Glycosylation; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D046911:Macromolecular Substances; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D004220:Disulfides; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell