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 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.
Tamura
N
N
Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Holroyd
K J
KJ
Banks
T
T
Kirby
M
M
Okayama
H
H
Crystal
R G
RG
D000328:Adult; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D004247:DNA; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012507:Sarcoidosis / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004247:DNA