T cell receptor delta gene repertoire and diversity of intestinal intraepithelial lymphocytes in athymic mice.

T cell receptor (TCR) delta gene rearrangements in intestinal intraepithelial lymphocytes (IEL) were studied in athymic radiation chimeras using polymerase chain reaction (PCR) and sequence analysis of DNAs spanning the variable (V), diversity (D), and junctional (J) genes. In both thymus-bearing and athymic mice, IEL delta gene rearrangements occurred for V delta 3, V delta 4, V delta 5 and V delta 6. V-D-J junctional-site sequence analyses of cloned DNAs from rearranged IEL delta genes in athymic mice revealed a predominance of in-frame rearrangements; junctional diversity consisting of nucleotide removal from V, D and/or J genes; N segment nucleotide insertions; and high overall gene diversity. Evaluation of PCR-amplified cDNAs made from IEL RNA indicated that all four rearranged V delta genes were expressed in IEL from athymic mice. The high diversity observed at the gene level also was present in amino acid sequences encoded by the V-D-J region of IEL delta genes in athymic mice. These data demonstrate that there is extensive diversity of rearranged delta genes in IEL which develop extrathymically, and suggest that the delta chain of IEL TCR-gamma delta+ T cells has the potential for interactions with polymorphic structures.