DIVERSITY IN JUNCTIONAL SEQUENCES ASSOCIATED WITH THE COMMON HUMAN V-GAMMA-9 AND V-DELTA-2 GENE SEGMENTS IN NORMAL BLOOD AND LUNG COMPARED WITH THE LIMITED DIVERSITY IN A GRANULOMATOUS-DISEASE

The T cell receptor. (TCR) junctional regions (N regions) of the common human Vγ9 and Vδ2 gene segments were sequenced from the blood and lung of normal individuals (195 transcripts) and a group of individuals with sarcoidosis (220 transcripts), a granulomatous disease in which increased numbers of Vγ9+ γ/δ T cells are often observed. In normal individuals, the vast majority (86%) ofblood Vγ9 transcripts used the JyP gene segment. In contrast to this restriction ofJ region usage, there was a large diversity of the junctional region, with <20% of blood Vγ9 junctional regions showing identical sequences for any one normal individual. For the blood Vδ2 transcripts in normal individuals, there was restriction of J region usage, with 93% using Jδ1. Thejunctional regions were even more diverse than for Vγ9, with a unique sequence observed in each transcript examined. Compared with blood, sequences from the normal lung showed a small increase in identical junctional regions, particularly in.one individual where 46% of Vγ9 transcripts examined were identical, suggesting a response of some γ/δ T cells to antigens found in the lung in the normal state. In marked contrast to normals, some individuals with sarcoidosis had large numbers of Vγ9 transcripts, as well as Vγ2 transcripts, sharing identical sequences. For Vγ9 blood transcripts, two individuals showed 84 and 56% ofjunctional region sequences to be identical, respectively. Similarly, blood Vγ2 transcripts showed 43, 33, and 25% identical junctional region sequences in three individuals. In the sarcoid patient with the most striking over-representation of blood Vγ9junctional sequences, lung Vy9 transcripts showed increased (67%) use of the same junctional region sequence as in blood. This limited diversity of TCR junctional regions among some individuals with sarcoidosis suggests a response from specific stimuli, possibly antigenic, and that γ/δ T cells may play a specific role in granuloma formation in sarcoidosis, as has been suggested in other granulomatous diseases. © 1990, Rockefeller University Press., All rights reserved.