Localization of a T-cell receptor diversity-region element

Abstract

Recently, complementary DNA clones encoding one chain of the T-cell receptor for antigen have been isolated from both murine and human cell lines^1–3. Sequence analysis of these clones indicates that they encode elements analogous to the variable (V), constant (C) and joining (J) regions of immunoglobulins^2,3 and that this corresponds to the β-chain subunit of the T-cell receptor complex⁴. These genes are rearranged in the genomes of specific T-cell lines and hybrids but not in other cell types¹. Analysis of the components of one such rearranged gene, 2B4, isolated from the pigeon cytochrome c-specific, H–2E-restricted T helper (T_H) hybridoma⁵, 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 segments⁶. As this sequence lies at a similar position to the diversity (D) region in immunoglobulin heavy-chain genes⁷, we postulated the existence of an array of germ-line D-region elements that would contribute significantly to the number of different β-chain molecules which could be created. Here we describe the localization and sequence of one such D-region element, found ∼650 nucleotides 5′ to the first J_T cluster⁸. This element seems to be involved in both functional (V–D–J) and non-functional (D–J) rearrangements. Our observations, combined with previous results^6,8,9, indicate that variable-region formation (V–D–J joining) in the T-cell receptor β-chain gene follows the 12/23-base pair (bp) rule of rearrangement established for the recombination of immunoglobulin gene segments^7,10, but that the organization of the heptamer and non-amer element found surrounding the D region is significantly different.