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.
| Publication Type | Academic Article |
| Authors | Tamura N, Holroyd K, Banks T, Kirby M, Okayama H, Crystal R |
| Journal | J Exp Med |
| Volume | 172 |
| Issue | 1 |
| Pagination | 169-81 |
| Date Published | 07/01/1990 |
| ISSN | 0022-1007 |
| Keywords | Lung, Receptors, Antigen, T-Cell, Sarcoidosis, T-Lymphocytes |
| Abstract | The T cell receptor (TCR) junctional regions (N regions) of the common human V gamma 9 and V delta 2 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 V gamma 9+ gamma/delta + T cells are often observed. In normal individuals, the vast majority (86%) of blood V gamma 9 transcripts used the J gamma P gene segment. In contrast to this restriction of J region usage, there was a large diversity of the junctional region, with less than 20% of blood V gamma 9 junctional regions showing identical sequences for any one normal individual. For the blood V delta 2 transcripts in normal individuals, there was restriction of J region usage, with 93% using J delta 1. The junctional regions were even more diverse than for V gamma 9, 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 V gamma 9 transcripts examined were identical, suggesting a response of some gamma/delta 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 V gamma 9 transcripts, as well as V delta 2 transcripts, sharing identical sequences. For V gamma 9 blood transcripts, two individuals showed 84 and 56% of junctional region sequences to be identical, respectively. Similarly, blood V delta 2 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 V gamma 9 junctional sequences, lung V gamma 9 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 gamma/delta T cells may play a specific role in granuloma formation in sarcoidosis, as has been suggested in other granulomatous diseases. |
| DOI | 10.1084/jem.172.1.169 |
| PubMed ID | 2141626 |
| PubMed Central ID | PMC2188169 |