A Chromosomal Inversion Generates a Functional T Cell Receptor β Chain Gene

Abstract

T-cell antigen receptors are disulfide-linked heterodimers constituted of two chains denoted α and β. As in the immunoglobulins, each chain is coded by a variable (V) and a constant (C) gene. The Vβ gene is composed of three gene segments designated variable (Vβ), diversity (Dβ) and joining (Jβ). The V, D and J gene segments are separate in the germline and brought together by DNA-rearrangements during T-lymphocyte differentiation to form a complete V gene. Before somatic rearrangements, the 3’ side of the Vβ gene segments, the 5’ side of the Jβgene segments and both sides of the Dβ gene segments are flanked by recognition sequences for DNA rearrangement. These recombination signal sequences are comprised of three components -a conserved heptamer, a non-conserved spacer sequence of 12 or 23 nucleotides and a conserved A/T rich nonamer. As in immunoglobulin genes, DNA rearrangement occurs only when one gene segment has a 12 base pair spacer sequence and the second has a 23 nucleotide spacer sequence.