Localization of a T-cell receptor diversity-region element.

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.