Biology Reference
In-Depth Information
constant domain ( Haas et al., 1993; Raulet, 1989). The structure of human gd
TCR resembles that of the ab TCR in that they organize each V and C domain
into immunoglobulin ( Ig)-like folds linked by intradomain disul®de bonding
( Li et al., 1998). The V domains are subdivided into framework and hyper-
variable regions with surface-exposed complementary determining regions
(CDRs) ( Li et al., 1998). The structure of the gd TCR is much closer to that of
the ab TCR than to the structure of the Ig receptor. Although several structural
features are common to both types of TCR, gd TCR have distinctive properties.
The gd TCR has charged amino acid substitutions in particular positions of the
Vg and Vd chains and uses corresponding alignments in CDR1 and CDR2 of
di¨erent subfamilies of Vg and Vd chains. These special alignments may deter-
mine the restricted g=d chain pairing characteristic of gd TCRs (Arden et al.,
1995a,b). In addition, gd TCRs show a higher divergence in the CDR1 and
CDR2 regions than ab TCRs and this may expand the diversity of the reper-
toire of gd TCR. ab TCRs are constrained in the CDR1 and CDR2 by the re-
quirement for the binding to MHC molecules (Chien and Davis, 1993; Garcia
et al., 1996). Perhaps the most interesting di¨erence between ab and gd TCR
structure is the diversi®cation of the CDR3 region length and sequence vari-
ability exhibited by gd TCRs ( Davis and Bjorkman, 1988; Rock et al., 1994).
CDR3 loops are of particular interest because they represent the site of peptide/
antigen contact and recognition ( Davis and Bjorkman, 1988; Engel and Hedrick,
1988). CDR3 of human TCRd are 8±21 amino acids long, whereas CDR3 of
TCRg are shorter (1±12 amino acids) but also variable in size ( Rock et al.,
1994). In contrast, CDR3 loops of TCR a and b chains are typically similar in
length (6±12 amino acids), re¯ecting the size constraints imposed by peptide
antigens bound to the MHC groove. The length variation in CDR3 g=d may
re¯ect greater heterogeneity in the size of gd T-cell ligands. In this sense, anti-
gen recognition by gd TCR may be more similar to Ig recognition of antigen
than to that of ab TCR recognition of the MHC-peptide complex (Chien et al.,
1996). The crystal structure of the human TCR Vd (Vd3-Dd2-Jd1) chain sug-
gests that its overall structure shares features of both ab TCR and Ig receptors,
both in the framework and CDR regions ( Li et al., 1998). It has been proposed
that these structural features may function to couple Ig-like recognition prop-
erties, such as recognition of native antigens, with cellular e¨ector functions,
such as target cell lysis or interferon (IFN )-g secretion (Sciammas et al., 1994).
Each chain of the gd TCR is encoded in di¨erent loci. The human g locus
(TCRG ) is located on chromosome 7 and consists of a series of V genes (Vg)
located 5
0
of two constant genes (TRGC Cg 1 and Cg 2), each one preceded
by J segments (TRGJ ), three upstream of Cg 1 and two located upstream of Cg
2 (Bensmana et al., 1991). The use of Cg1orCg2 gene segment determines
whether the gd heterodimer is disul®de linked or not (type 1 vs. type 2 respec-
tively) ( Lefranc and Rabbitts, 1989). There are no Dg segments. The Vg region
comprises 14 genes (TRGV six pseudogenes, eight functional genes). These
TRGV genes belong to four subfamilies ( I±IV ) whose members share amino
acid sequence homology. The Vg I subfamily consists of nine members, ®ve
