Identification of a novel pre-TCR isoform in which the accessibility of the TCR beta subunit is determined by occupancy of the 'missing' V domain of pre-T alpha.
We have identified a novel pre-TCR isoform that is structurally distinct from conventional pre-TCR complexes and whose TCR beta chains are inaccessible to anti-TCR beta antibodies. We term this pre-TCR isoform the MB (masked beta)-pre-TCR. Pre-T alpha (pT alpha) subunits of MB-pre-TCR complexes have a larger apparent mol. wt due to extensive modification with O:-linked carbohydrates; however, preventing addition of O-glycans does not restore antibody recognition of the TCR beta subunits of MB-pre-TCR complexes. Importantly, accessibility of TCR beta chains in MB-pre-TCR complexes is restored by filling in the 'missing' variable (V) domain of pT alpha with a V domain from TCR alpha. Moreover, the proportion of pre-TCR complexes in which the TCR beta subunits are accessible to anti-TCR beta antibody varies with the cellular context, suggesting that TCR beta accessibility is controlled by a trans-acting factor. The way in which this factor might control TCR beta accessibility as well as the physiologic relevance of TCR beta masking for pre-TCR function are discussed.
Berger
M A
MA
Immunobiology Working Group, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Carleton
M
M
Rhodes
M
M
Sauder
J M
JM
Trop
S
S
Dunbrack
R L
RL
Hugo
P
P
Wiest
D L
DL
D000818:Animals; D002240:Carbohydrate Sequence; D019281:Dimerization; D018014:Gene Transfer Techniques; D006031:Glycosylation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000302:isolation & purification; D017434:Protein Structure, Tertiary / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha