Biology Reference
In-Depth Information
port a more ancient origin for gd TCR genes ( Born et al., 1999; Hayday,
2000). gd TCR genes are present in all animal species, from cartilaginous ®sh
(Raja eglanteria, or skate) to mammals ( Born et al., 1999; Rast et al., 1997).
Although gd T cells are broadly distributed in all jawed vertebrate species, there
are signi®cant interspecies di¨erences in the genes that encode d and in partic-
ular g chains as well as in the anatomical distribution and abundance of gd T
cells (Anderson et al., 1995; Hayday et al., 1985; Lefranc and Rabbitts, 1989;
Lefranc et al., 1989; Six et al., 1996). For example, although gd T cells represent
only 1±5% of peripheral CD3
cells in primates and rodents, they are abundant
in the avian immune system and they account for up to 70% of circulating
CD3
T cells in young ruminants, decreasing to 5±25% with aging (Cooper et
al., 1989; Hein and Mackay, 1991). ab and gd T cells both use CD3 as an
activation coreceptor and both produce cytokines and express cytotoxic e¨ector
function (cytotoxic T lymphocytes, or CTL) upon TCR engagement. However,
ab and gd T cells di¨er in many important ways. First, in terms of tissue dis-
tribution, the majority of CD3
T cells in the peripheral blood and peripheral
lymphoid tissues in humans and mice express the ab TCR and only 1±5%
express the gd TCR. In contrast, the majority of gd TCR-bearing T cells are
found in epithelial tissues, such as the gut in humans (intestinal intraepithelial
lymphocytes, or IELs), and the skin and reproductive tract of mice ( Deusch
et al., 1991; Goodman and Lefrancois, 1988; Itohara et al., 1990; Stingl et al.,
1987).
Second, gd TCR show a more restricted diversity at the genetic level than ab
TCR. The number of Vg and Vd genes in the germ line, and therefore their
combinatorial diversity, is limited compared with the number of Va and Vb
genes. The use of genetic mechanisms, such as N-region diversi®cation among
others, increases the diversity of the gd TCR repertoire (Brenner et al., 1988;
Kabelitz, 1992; Lefranc and Rabbitts, 1989; LeFranc et al., 1986; Quertermous
et al., 1986a, b). Although the immune system can generate a broad and diverse
gd TCR repertoire, one of the most remarkable characteristics of the gd T-cell
population is the preferential usage of certain V region genes to form the TCR.
This bias toward the expression of certain V gene products in part de®nes the
tissue-speci®c restriction of certain gd TCRs. For example, two single variable
region genes (TCRGV2S1 and TCRDV102S1) encode the Vg9/Vd2 chains
found in >80% of peripheral blood gd T cells in adults ( Borst et al., 1989;
Bottino et al., 1988; Casorati et al., 1989; Kabelitz et al., 1991; Parker et al.,
1990; Triebel et al., 1988a, b). In contrast, Vd1 is preferentially expressed in
human spleen and thymus, whereas human IELs carry both Vd1 and Vd3
elements (De Libero et al., 1993; Peyrat et al., 1995; Porcelli et al., 1991).
The existence of canonical or homogeneous (identical V( D)J composition and
junctional sequences) TCRs has been described in mice and humans, adding to
the restriction of the gd repertoire ( Davodeau et al., 1993; McVay and Carding,
1999; Tamura et al., 1990).
Third, ab and gd T cells di¨er in the manner in which they recognize anti-
gens. Whereas ab T cells mainly recognize peptides presented by major histo-
