Comparison of the sequence of a cloned T cell-specific cDNA with those of cross-reacting cloned cDNAs isolated from a thymocyte library indicates the presence of variable, constant and joining regions remarkably similar in size and sequence to those encoding immunoglobulin proteins. Together with the evidence for somatic gene rearrangements reported in the accompanying paper, this strongly suggests that the TM86 cDNA clone encodes one chain of the T-cell receptor for antigen.

A putative T-cell receptor gene was isolated from the DNA of the helper hybridoma, 2B4 . Analysis of the sequence components of this rearranged gene indicates the presence of separate variable (V), diversity (D) and joining (J) region elements analogous to those of heavy-chain immunoglobulins. These findings further support the belief that the products of this locus are involved in antigen recognition by T cells. There is no evidence of somatic mutation between the putative germ-line and the expressed variable-region gene.

The genomic structure of the joining (J) and constant (C) regions of the locus encoding the beta-chain of the murine T-cell receptor has been analysed. The gene segments are arranged tandemly (J-C/J-C) within a 15-kilobase region. The two constant-region genes are almost identical, differing by only four amino acids, all in carboxy-terminal portions. Each C region comprises four exons encoding an external globular domain, a small hinge-like region, a transmembrane region and a cytoplasmic tail plus 3'-untranslated region. The two clusters of J regions each contain 7 distinct elements, 12 of which may be functional.

The Notch intracellular domain functions as a co‐activator for the DNA‐binding protein Suppressor of Hairless (Su(H)) to mediate myriad cell fate decisions. Notch pathway activity is balanced by transcriptional repression, mediated by Su(H) in concert with its Drosophila corepressor Hairless. We demonstrate that the Drosophila neural BEN‐solo protein Insensitive (Insv) is a nuclear factor that inhibits Notch signalling during multiple peripheral nervous system cell fate decisions. Endogenous Insv was particularly critical when repressor activity of Su(H) was compromised. Reciprocally, ectopic Insv generated several Notch loss‐of‐function phenotypes, repressed most Notch targets in the E(spl)‐C, and opposed Notch‐mediated activation of an E(spl)m3‐luc reporter. A direct role for Insv in transcriptional repression was indicated by binding of Insv to Su(H), and by strong chromatin immunoprecipitation of endogenous Insv to most E(spl)‐C loci. Strikingly, ectopic Insv fully rescued sensory organ precursors in Hairless null clones, indicating that Insv can antagonize Notch independently of Hairless. These data shed first light on the in vivo function for a BEN‐solo protein as an Su(H) corepressor in the Notch pathway regulating neural development.

Recently, complementary DNA clones encoding one chain of the T-cell receptor for antigen have been isolated from both murine and human cell lines. Sequence analysis of these clones indicates that they encode elements analogous to the variable (V), constant (C) and joining (J) regions of immunoglobins and that this corresponds to the beta-chain subunit of the T-cell receptor complex. These genes are rearranged in the genomes of specific T-cell lines and hybrids but not in other cell types. Analysis of the components of one such rearranged gene, 2B4, isolated from the pigeon cytochrome c-specific, H-2E-restricted T helper (TH) hybridoma, and its unrearranged (liver) counterpart, indicate that an 8-nucleotide sequence 3' to the rearranged variable region is not derived from either the germ-line V- or J-region gene segments. As this sequence lies at a similar position to the diversity (D) region in immunoglobulin heavy-chain genes, we postulated the existence of an array of germ-line D-region elements that would contribute significantly to the number of different beta-chain molecules which could be created. Here we describe the localization and sequence of one such D-region element, found approximately 650 nucleotides 5' to the first JT cluster. This element seems to be involved in both functional (V-D-J) and non-functional (D-J) rearrangements. Our observations, combined with previous results, indicate that variable-region formation (V-D-J joining) in the T-cell receptor beta-chain gene follows the 12/23-base pair (bp) rule of rearrangement established for the recombination of immunoglobulin gene segments, but that the organization of the heptamer and nonamer element found surrounding the D region is significantly different.