Identification of a novel pre-TCR isoform in which the accessibility of the TCRβ subunit is determined by occupancy of the 'missing' V domain of pre-Tα

We have identified a novel pre-TCR isoform that is structurally distinct from conventional pre-TCR complexes and whose TCRβ chains are inaccessible to anti-TCRβ antibodies. We term this pre-TCR isoform the MB (masked β)-pre-TCR. Pre-Tα (pTα) 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 TCRβ subunits of MB-pre-TCR complexes. Importantly, accessibility of TCRβ chains in MB-pre-TCR complexes is restored by filling in the 'missing' variable (V) domain of pTα with a V domain from TCRα. Moreover, the proportion of pre-TCR complexes in which the TCRβ subunits are accessible to anti-TCRβ antibody varies with the cellular context, suggesting that TCRβ accessibility is controlled by a trans-acting factor. The way in which this factor might control TCRβ accessibility as well as the physiologic relevance of TCRβ masking for pre-TCR function are discussed.