T-CELL RECEPTOR DELTA-GENE REPERTOIRE AND DIVERSITY OF INTESTINAL INTRAEPITHELIAL LYMPHOCYTES IN ATHYMIC MICE

T cell receptor (TCR) delta gene rearrangements in intestinal intraepi thelial lymphocytes (IEL) were studied in athymic radiation chimeras u sing polymerase chain reaction (PCR) and sequence analyses of DNAs spa nning the variable (V), diversity (D), and junctional (J) genes. In bo th thymus-bearing and athymic mice, IEL delta gene rearrangements occu rred for V(delta3), V(delta4), V(delta5) and V(delta6). V-D-J junction al-site sequence analyses of cloned DNAs from rearranged IEL delta gen es in athymic mice revealed a predominance of in-frame rearrangements; junctional diversity consisting of nucleotide removal from V, D and/o r J genes; N segment nucleotide insertions; and high overall gene dive rsity. Evaluation of PCR-amplified cDNAs made from IEL RNA indicated t hat all four rearranged V(delta) genes were expressed in IEL from athy mic mice. The high diversity observed at the gene level also was prese nt in amino acid sequences encoded by the V-D-J region of IEL delta ge nes in athymic mice. These data demonstrate that there is extensive di versity of rearranged delta genes in IEL which develop extrathymically , and suggest that the delta chain of IEL TCR-gammadelta+ T cells has the potential for interactions with polymorphic structures.