Biology Reference
In-Depth Information
functional genes and four pseudogenes; the other three subfamilies contain only
one member each and there are two pseudogenes that do not belong to any of
these subfamilies. Di¨erent nomenclature has been proposed for designating
human TCR genes. The WHO-IUIS Nomenclature Subcommittee on TCR
Designation (WHO-IUIS, 1995) and the International ImMunoGeneTics data-
base (IMGT, URL available at http://imgt.cnusc.fr:8104) is the one currently
used the most (Arden et al., 1995a; Lefranc et al., 1998, 1999).
The human TCRd (TCRD) genes are located on chromosome 14 within the
TCRa (TCRA) locus, between the Va and the Ja gene segments (Griesser et al.,
1988; Satyanarayana et al., 1988). The Vd genes are actually interspersed with
Va gene segments ( Loh et al., 1988; McVay and Carding, 1999; Miossec et al.,
1991; Takihara et al., 1989a, b). Eight human Vd genes (TRDV ) have been
described. Vd1 and Vd2 genes are located 5
0
of Dd segments and Vd3 is down-
stream of Cd in an inverted transcriptional orientation ( Hata et al., 1989;
Takihara et al., 1989a). Vd4toVd8 are members of the Va gene families and
can rearrange either with Ja and Ca or Jd and Cd segments to form TCR-a or
TCR-d chains, respectively. The TCR-d locus is completed with three Dd
(TRDD Dd1±3) segments, four Jd (TRDJ Jd1±4) segments and a single Cd
segment (TRDC ) ( Davodeau et al., 1994; Loh et al., 1988; Takihara et al.,
1988).
The limited number of germ-line V genes and D and J segments is the cause
of the low combinatorial diversity of the gd TCRs compared with the ab TCRs
(Davis and Bjorkman, 1988). The gd TCR repertoire is even more restricted by
preferential V gene usage. However, it has been estimated that the potential
number of di¨erent gd TCRs in mice actually exceeds (10
20
) that of ab TCRs
(10
15
) or B-cell Ig receptors (10
11
) (McVay and Carding, 1999). The main
mechanisms that account for the diversi®cation of gd TCRs include: a) diversi-
®cation of the N region (nucleotide insertion and modi®cation of TRDV-( D)-J
junctional sequences); b) translation of the D region in three di¨erent read-
ing frames in the d chain; and c) use of multiple contiguous D segments to form
the d chain ( Kabelitz, 1992; LeFranc et al., 1986; Sturm et al., 1989). Conse-
quently, the antigen repertoire of gd T cells is potentially greater than that for
ab T cells. To what extent this diversity is used by gd TCRs is not known.
ORIGIN AND DISTRIBUTION OF
gd
T CELLS
Ontogeny of Human
gd
T Cells
Prenatal development of gd T cells in humans can be divided into two phases:
prethymic phase (before thymic development by the 8th week of gestation) and
intrathymic phase (after thymic development, 8th week). gd T cells are gen-
erated before the 8th week of gestation in two sites: fetal liver and primitive
intestine (McVay and Carding, 1996; McVay et al., 1998; Wucherpfennig et
al., 1993). Productive gene rearrangements and transcripts of both Vg and Vd
