SummaryThe T cell receptor. (TCR) junctional regions (N regions) of the common human Vy9 and V62 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 Vy9+ -y/b+ T cells are often observed. In normal individuals, the vast majority (86%) ofblood Vy9 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 Vy9 junctional regions showing identical sequences for any one normal individual. For the blood V62 transcripts in normal individuals, there was restriction of J region usage, with 93% using J61. The junctional regions were even more diverse than for Vy9, 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 Vy9 transcripts examined were identical, suggesting a response of some y/6 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 Vy9 transcripts, as well as VS2 transcripts, sharing identical sequences . For Vy9 blood transcripts, two individuals showed 84 and 56% ofjunctional region sequences to be identical, respectively. Similarly, blood VS2 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 Vy9junctional 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 y/6 T cells may play a specific role in granuloma formation in sarcoidosis, as has been suggested in other granulomatous diseases.