Expansion of circulating V gamma 9/V delta 1 T cells in a patient with a syndrome of recurrent fever: evidence for an unusual antigen-driven process leading to selection of recurrent motifs within TCR junctional loops of diverse lengths
F. Jouen-beades et al., Expansion of circulating V gamma 9/V delta 1 T cells in a patient with a syndrome of recurrent fever: evidence for an unusual antigen-driven process leading to selection of recurrent motifs within TCR junctional loops of diverse lengths, EUR J IMMUN, 29(10), 1999, pp. 3338-3349
Polyclonal expansions of human V delta 1 T cells have been described in div
erse physiopathological situations without strong TCR structural data for a
n antigen-driven selection. Here, we have analyzed the phenotype and TCR re
pertoire of gamma delta T cells obtained from the peripheral blood of a 19-
year-old patient with a syndrome of recurrent fever, which accounted for up
to 40 % of CD3(+) T cells and expressed predominantly V gamma 9 and V delt
a 1 TCR regions and a memory phenotype. Sequence analysis of V delta 1-J de
lta 1 transcripts derived from peripheral blood lymphocytes (PBL) indicated
that, while V delta 1-J delta 1 junctional sequences were diverse in lengt
h, all but one contained several recurrent motifs at conserved positions fr
om both the 5'- and 3'-ends of the complementarity-determining region (CDR)
3 loop. Analysis of gamma delta T cell clones derived from patient PBL demo
nstrated that V gamma 9(+) but not V gamma 9(-) T cell clones frequently ex
pressed V delta 1 chains with these characteristics and unveiled a hierarch
y between the constraints imposed on the 5'- vs. the 3' motifs of the V del
ta 1 CDR3 loops. These results constitute the first strong evidence for a n
ominal antigen-driven selection of V delta 1 T cells in vivo and also sugge
st that the hierarchy of the constraints imposed by antigens respectively o
n the length and amino acid composition of TCR CDR3 loops differs between a
lpha beta and gamma delta T cells.