Rearrangement of two distinct T-cell γ-chain variable-region genes in human DNA

Abstract

Selective cloning procedures for T-cell-specific complementary DNAs have revealed the existence of a gene designated¹ γ as well as the main antigen receptor α- and β-chain genes^2–10. The γ-chain genes undergo rearrangement during T-cell differentiation but the patterns and complexity of such rearrangements differ markedly in mouse^11–13 and human¹⁴. In mouse, a panel of cytotoxic T-lymphocyte clones exhibit the same rearrangement pattern with a γ-chain gene probe¹¹ and a set of three γ-chain variable (V) genes have been identified in the DNA¹². Clonal diversity in mouse seems to be confined to V–J (joining) regions¹¹. In contrast, human T-cell lines exhibit diverse rearrangements¹⁴ suggestive of a family of differing V_γ genes variously rearranging to the two γ-chain constant (C) region genes^14,15. Here we report the cloning of two very different V_γ genes rearranged to J segments upstream of the two human C_γ genes. Both V_γ genes are rearranged productively but nucleotide sequence comparison shows that they possess very little homology with each other. This shows that human T-cell V_γ genes exist which differ significantly from each other at the nucleotide level and that such diverse genes can be usefully rearranged in different T cells.