230
6 Immunoproteins
chain of 13 kDa, and class II molecules, consisting of two non-covalently bound glycosylated
chains of 32-34 kDa. Class II genes, but not
those of class I, are expressed in the tadpole.
Gene sequences for both classes of MHC antigen
have been identified in the carp Cyprinus carpio
[49, 69, 110]. There is even some evidence for the
existence of an MHC in a tunicate, the ascidian
Botryllus sp. [49].
~2m is found both free in the body fluids and
associated with the MHC antigen on the cell surface. It is a non-glycosylated protein of 1213 kDa which shows up to 40 % difference in pairwise comparisons of its sequence of 99-100 amino
acids between humans and various other mammals [61]. ~2m is ubiquitous in the vertebrates but
has rarely been examined in the lower vertebrates
[36, 61]. ~2m-like proteins have also been
detected immunologically on haemocytes of the
earthworm Lumbricus terrestris, on tissue culture
cells of Drosophila melanogaster, and on other
invertebrate cells [17]. MHC molecules of class I
in the membranes of vertebrate cells occur mostly
bound to ~2m, but can also serve as the anchor for
other proteins. For example, the tetrameric insulin receptor in human cell cultures has been
shown to be associated with class I molecules.
Thus, the range of functions for MHC molecules
has expanded in unexpected directions [43].
6.5 Cytokines and Interferons
The complex interactions between B lymphocytes, T cells and macrophages involve the activity
of regulatory polypeptides which have become
known as "lymphokines" or "interleukins". It
soon became apparent that the same, or similar,
polypeptides function not only as regulators of
the immune system but also as hormone-like
growth and differentiation factors. They are
involved, for example, in the control of haematopoiesis and the conversion of the pluripotent stem
cells of the bone marrow into blood cells, such
as erythrocytes, granulocytes, monocytes and
lymphocytes, and into certain tissue cells, like
macrophages, mast cells and dendritic cells. They
control inflammation processes in that they react
chemotactically with neutrophils or macrophages,
and they stimulate hepatocytes to produce acutephase proteins. In view of these multiple activities, the general term "cytokines" was introduced. Cells stimulated by cytokines in turn
produce further mediators; a cytokine network
serves to connect functionally lymphocytes, macrophages and haematopoietic cells. About 50
cytokines are presently known. They include, for
example, the interleukins, of which eight have
been described (IL-1 to IL-8) , although some
authors count 11 [56, 134], interferon IPN-y,
growth factors such as epidermal growth factor
(EGF) and PDGF, colony-stimulating factors
(CSFs), tumour necrosis factors and erythropoietin [6, 39, 114]. The cytokinins function by binding to specific receptors on the cell surface; these
may be grouped into families on the basis of
structural similarity. The IL-1 and PDGF receptors belong to the Ig super-family. The receptors
for 11-2, -3, -4, -6 and -7, various CSFs and
erythropoietin, as well as growth hormone and
prolactin all possess corresponding modules of
200 amino acids with four cysteine residues in the
N-terminal half and the sequence WSXWS close
to the C-terminus. The binding domains of the
receptors for interferons a-y and the receptor for
the clotting factor VII (known as tissue factor)
have the same structure, a sequence of 210 amino
acids with characteristic cysteine pairs at both the
C- and the N-terminii. The latter two receptor
families show similarities to the Ig homology
units in their tertiary structure, despite having different amino acid sequences [7].
Interleukin-l (IL-1) was discovered as a product of activated macrophages, but is also formed
by other cells such as fibroblasts, keratinocytes
and B cells. It is actually a whole family of proteins which are involved in various reactions to
injury and infection: thymocyte proliferation, B
cell activation, multiplication of the neutrophilic
granulocytes, synthesis of acute-phase proteins in
the liver, and triggering of fever [6]. 11-1 activities
have been detected in all classes of vertebrates
including fish; they are usually bound to proteins
of 12-20 kDa but sometimes to larger proteins of
35-70 kDa. IL-1-like proteins have also been
detected in the starfish Asterias forbesi and various ascidians [9]. There are two different proteins
of this family in man and other mammals (IL-1a
and IL-1~); they have identical activities and bind
to the same receptors but agree by only 26 % in
their sequences. Both arise from precursors of
about 270 amino acids by cleavage of the Nterminal 112-116 amino acids. The cD NA or gene
sequences are known for several species; the
common gene structure of seven exons indicates
that IL-1a and -1~, despite the poor similarity of
their amino acid sequences, arose by duplication
from a common ancestral gene [6].
6 Immunoproteins
chain of 13 kDa, and class II molecules, consisting of two non-covalently bound glycosylated
chains of 32-34 kDa. Class II genes, but not
those of class I, are expressed in the tadpole.
Gene sequences for both classes of MHC antigen
have been identified in the carp Cyprinus carpio
[49, 69, 110]. There is even some evidence for the
existence of an MHC in a tunicate, the ascidian
Botryllus sp. [49].
~2m is found both free in the body fluids and
associated with the MHC antigen on the cell surface. It is a non-glycosylated protein of 1213 kDa which shows up to 40 % difference in pairwise comparisons of its sequence of 99-100 amino
acids between humans and various other mammals [61]. ~2m is ubiquitous in the vertebrates but
has rarely been examined in the lower vertebrates
[36, 61]. ~2m-like proteins have also been
detected immunologically on haemocytes of the
earthworm Lumbricus terrestris, on tissue culture
cells of Drosophila melanogaster, and on other
invertebrate cells [17]. MHC molecules of class I
in the membranes of vertebrate cells occur mostly
bound to ~2m, but can also serve as the anchor for
other proteins. For example, the tetrameric insulin receptor in human cell cultures has been
shown to be associated with class I molecules.
Thus, the range of functions for MHC molecules
has expanded in unexpected directions [43].
6.5 Cytokines and Interferons
The complex interactions between B lymphocytes, T cells and macrophages involve the activity
of regulatory polypeptides which have become
known as "lymphokines" or "interleukins". It
soon became apparent that the same, or similar,
polypeptides function not only as regulators of
the immune system but also as hormone-like
growth and differentiation factors. They are
involved, for example, in the control of haematopoiesis and the conversion of the pluripotent stem
cells of the bone marrow into blood cells, such
as erythrocytes, granulocytes, monocytes and
lymphocytes, and into certain tissue cells, like
macrophages, mast cells and dendritic cells. They
control inflammation processes in that they react
chemotactically with neutrophils or macrophages,
and they stimulate hepatocytes to produce acutephase proteins. In view of these multiple activities, the general term "cytokines" was introduced. Cells stimulated by cytokines in turn
produce further mediators; a cytokine network
serves to connect functionally lymphocytes, macrophages and haematopoietic cells. About 50
cytokines are presently known. They include, for
example, the interleukins, of which eight have
been described (IL-1 to IL-8) , although some
authors count 11 [56, 134], interferon IPN-y,
growth factors such as epidermal growth factor
(EGF) and PDGF, colony-stimulating factors
(CSFs), tumour necrosis factors and erythropoietin [6, 39, 114]. The cytokinins function by binding to specific receptors on the cell surface; these
may be grouped into families on the basis of
structural similarity. The IL-1 and PDGF receptors belong to the Ig super-family. The receptors
for 11-2, -3, -4, -6 and -7, various CSFs and
erythropoietin, as well as growth hormone and
prolactin all possess corresponding modules of
200 amino acids with four cysteine residues in the
N-terminal half and the sequence WSXWS close
to the C-terminus. The binding domains of the
receptors for interferons a-y and the receptor for
the clotting factor VII (known as tissue factor)
have the same structure, a sequence of 210 amino
acids with characteristic cysteine pairs at both the
C- and the N-terminii. The latter two receptor
families show similarities to the Ig homology
units in their tertiary structure, despite having different amino acid sequences [7].
Interleukin-l (IL-1) was discovered as a product of activated macrophages, but is also formed
by other cells such as fibroblasts, keratinocytes
and B cells. It is actually a whole family of proteins which are involved in various reactions to
injury and infection: thymocyte proliferation, B
cell activation, multiplication of the neutrophilic
granulocytes, synthesis of acute-phase proteins in
the liver, and triggering of fever [6]. 11-1 activities
have been detected in all classes of vertebrates
including fish; they are usually bound to proteins
of 12-20 kDa but sometimes to larger proteins of
35-70 kDa. IL-1-like proteins have also been
detected in the starfish Asterias forbesi and various ascidians [9]. There are two different proteins
of this family in man and other mammals (IL-1a
and IL-1~); they have identical activities and bind
to the same receptors but agree by only 26 % in
their sequences. Both arise from precursors of
about 270 amino acids by cleavage of the Nterminal 112-116 amino acids. The cD NA or gene
sequences are known for several species; the
common gene structure of seven exons indicates
that IL-1a and -1~, despite the poor similarity of
their amino acid sequences, arose by duplication
from a common ancestral gene [6].