228
6 Immunoproteins
6.3 T Cell Receptors
T cells recognize antigens only when they are presented on other cells together with an MHC antigen (MHC restriction); cytotoxic T cells are specific for the class I MHC products which are
found on most cells of the body, and T helper cells
are specific for the class II MHC products which
are produced by the APCs. Specific glycoproteins
present on the surface of the T cell are apparently
responsible for this MHC restriction: CD4 for the
MHC class II-specific T cells, and the heterodimeric CD8 for the class I-specific cells; both
belong to the immunoglobulin super-family [127].
The antigen-specific receptor of the T cell is a
heterodimer of the subunits a. and ~. A minor
proportion of the cells express receptor dimers
from two other chains, y and (). A third class of
T cell receptor is found in the chicken [32]. The
a.~ or y() receptor dimers are associated with the
CD3 complex, which is composed of four or five
different types of subunit according to the formula Y()EE;; or Y()EE;lJ. The E subunit is present
twice; ; is present either as a homodimer or as a
heterodimer with the homologous lJ chain [16].
With the exception of ; and lJ, all polypeptides of
the 1: cell receptor complex belong to the Ig superfamily [196]. The a. and ~ subunits are both about
40-50 kDa and have an N-terminal, variable V
domain and a C-terminal, relatively conserved C
domain; each domain corresponds to one Ig
homology unit (Fig. 6.2). The variable V domains
of the a and ~ chains together make up the
antigen-binding site.
The four receptor subunits a......() in man and in
the mouse are encoded by gene families which,
like the immunoglobulins, include a large number
of tandemly arranged V, J and C gene segments;
the ~ and () families also contain D segments. Furthermore, as for the immunoglobulins, the complete gene arises by somatic rearrangements of
V-(D)-J-C. The gene segments are flanked by
nonamer and heptamer sequences which are
almost completely identical with those of the
immunoglobulins [38]. The V~ domain consists of
about 109 amino acids. The murine V~ genes can
be divided into several subfamilies of one to three
members, and there are also many subfamilies of
human V~ genes. The sequence similarity of
members of the same subfamily in different species, e.g. man and the mouse, is often greater
than that between the subfamilies within the
same species, i.e. the subfamilies are apparently
very old [74, 128, 186]. The two murine C~ genes
are each made up of four exons; the first codes
for the extracellular, Ig-homologous domain of
125 amino acids, and the others for the hinge
sequence with 6, the transmembrane region with
36, and the cytoplasmic tail with 6 amino acids.
The two C~ sequences differ in only 5 of their 173
amino acids and therefore arose quite recently by
gene duplication [74]. '!\vo C~ genes are found
also in man and several rabbit varieties; other
rabbits possess three C~ genes [104]. The only
T cell receptor subunit of a non-mammal to be
sequenced (in this case via the cDNA) is the ~
chain of the chicken. Although there is only about
31 % agreement in the amino acid sequence, a
whole series of conserved structural features are
recognizable [188].
Thy-! also belongs to the immunoglobulin
super-family and is involved with the differentiation of thymocytes to mature T lymphocytes.
Many more Thy-l molecules are present on
mouse and rat than on canine thymocytes; they
are not present on human thymocytes or on
mature rat T lymphocytes, but in all species they
are found on neuronal brain cells, fibroblasts and
some other cell types. In the mouse and rat, the
molecule is a glycoprotein with a polypeptide
chain of 111 amino acids, the molecular mass of
which is increased from 12.5 to 17.5 kDa in the
brain and to 18.7 kDa in the thymus by the addition of three N-linked carbohydrate chains. The
Thy-l C-terminus in the rat brain is attached to
the cell membrane via glycosyl-phosphatidylinositol. This method of anchoring the membrane
proteins is found widely in unicellular eukaryotes
but is very rare in the vertebrates [73]. Thy-l has
the typical three-dimensional structure of an Ig
homology unit and agrees by 36 % with the amino
acid sequence of the murine VL chain [109]. Proteins resembling Thy-l have also been found, for
example, in lower chordates (ascidians), insects,
annelids and molluscs [17, 36, 109, 158].
6.4 MHC Antigens and ~2-MicrogIobulins
The proteins encoded by the major histocompatibility complex (MHC) may be divided into three
classes according to their structure and function.
MHC antigens of classes I and II are integral
membrane proteins which are responsible not
only for transplant rejection but also for the general differentiation between "self' and "non-self'
by the immune system. As described above, the T
lymphocytes recognize the complementary for-
6 Immunoproteins
6.3 T Cell Receptors
T cells recognize antigens only when they are presented on other cells together with an MHC antigen (MHC restriction); cytotoxic T cells are specific for the class I MHC products which are
found on most cells of the body, and T helper cells
are specific for the class II MHC products which
are produced by the APCs. Specific glycoproteins
present on the surface of the T cell are apparently
responsible for this MHC restriction: CD4 for the
MHC class II-specific T cells, and the heterodimeric CD8 for the class I-specific cells; both
belong to the immunoglobulin super-family [127].
The antigen-specific receptor of the T cell is a
heterodimer of the subunits a. and ~. A minor
proportion of the cells express receptor dimers
from two other chains, y and (). A third class of
T cell receptor is found in the chicken [32]. The
a.~ or y() receptor dimers are associated with the
CD3 complex, which is composed of four or five
different types of subunit according to the formula Y()EE;; or Y()EE;lJ. The E subunit is present
twice; ; is present either as a homodimer or as a
heterodimer with the homologous lJ chain [16].
With the exception of ; and lJ, all polypeptides of
the 1: cell receptor complex belong to the Ig superfamily [196]. The a. and ~ subunits are both about
40-50 kDa and have an N-terminal, variable V
domain and a C-terminal, relatively conserved C
domain; each domain corresponds to one Ig
homology unit (Fig. 6.2). The variable V domains
of the a and ~ chains together make up the
antigen-binding site.
The four receptor subunits a......() in man and in
the mouse are encoded by gene families which,
like the immunoglobulins, include a large number
of tandemly arranged V, J and C gene segments;
the ~ and () families also contain D segments. Furthermore, as for the immunoglobulins, the complete gene arises by somatic rearrangements of
V-(D)-J-C. The gene segments are flanked by
nonamer and heptamer sequences which are
almost completely identical with those of the
immunoglobulins [38]. The V~ domain consists of
about 109 amino acids. The murine V~ genes can
be divided into several subfamilies of one to three
members, and there are also many subfamilies of
human V~ genes. The sequence similarity of
members of the same subfamily in different species, e.g. man and the mouse, is often greater
than that between the subfamilies within the
same species, i.e. the subfamilies are apparently
very old [74, 128, 186]. The two murine C~ genes
are each made up of four exons; the first codes
for the extracellular, Ig-homologous domain of
125 amino acids, and the others for the hinge
sequence with 6, the transmembrane region with
36, and the cytoplasmic tail with 6 amino acids.
The two C~ sequences differ in only 5 of their 173
amino acids and therefore arose quite recently by
gene duplication [74]. '!\vo C~ genes are found
also in man and several rabbit varieties; other
rabbits possess three C~ genes [104]. The only
T cell receptor subunit of a non-mammal to be
sequenced (in this case via the cDNA) is the ~
chain of the chicken. Although there is only about
31 % agreement in the amino acid sequence, a
whole series of conserved structural features are
recognizable [188].
Thy-! also belongs to the immunoglobulin
super-family and is involved with the differentiation of thymocytes to mature T lymphocytes.
Many more Thy-l molecules are present on
mouse and rat than on canine thymocytes; they
are not present on human thymocytes or on
mature rat T lymphocytes, but in all species they
are found on neuronal brain cells, fibroblasts and
some other cell types. In the mouse and rat, the
molecule is a glycoprotein with a polypeptide
chain of 111 amino acids, the molecular mass of
which is increased from 12.5 to 17.5 kDa in the
brain and to 18.7 kDa in the thymus by the addition of three N-linked carbohydrate chains. The
Thy-l C-terminus in the rat brain is attached to
the cell membrane via glycosyl-phosphatidylinositol. This method of anchoring the membrane
proteins is found widely in unicellular eukaryotes
but is very rare in the vertebrates [73]. Thy-l has
the typical three-dimensional structure of an Ig
homology unit and agrees by 36 % with the amino
acid sequence of the murine VL chain [109]. Proteins resembling Thy-l have also been found, for
example, in lower chordates (ascidians), insects,
annelids and molluscs [17, 36, 109, 158].
6.4 MHC Antigens and ~2-MicrogIobulins
The proteins encoded by the major histocompatibility complex (MHC) may be divided into three
classes according to their structure and function.
MHC antigens of classes I and II are integral
membrane proteins which are responsible not
only for transplant rejection but also for the general differentiation between "self' and "non-self'
by the immune system. As described above, the T
lymphocytes recognize the complementary for-