Interleukin-2 (IL-2) is secreted by T helper
cells in cooperation with foreign antigens and IL1; it induces the proliferation of T cells and their
production of y-interferon. IL-2 has so far not
been unambiguously detected in birds and lower
vertebrates and shows large variation in immunological and functional characters amongst the
mammals. Human and bovine pre-IL-2, including
the 20 residues of the signal peptide, have lengths
of 153 and 155 amino acids, respectively; in the
rat, there are 169 amino acids, including a unique
sequence of 12 consecutive glutamines. There is
one N-linked carbohydrate chain in the bovine
IL-2 and two in the human and rat forms. The
sequences of IL-2 agree in these three species in
60-65 % of positions [31]. Interleukin-3 (IL-3) is
mainly produced by antigen-stimulated T cells
and stimulates the formation of all the blood cell
types originating in the stem cells of the bone
marrow. Rat IL-3 differs from the murine form in
46 % of its amino acids and has only a limited
effect on murine bone marrow cells. Surprisingly,
the sequence agreement in the flanking NT regions (90 %) and the four introns (80 %) is greater
than in the exons (76 %) of these species [35].
There are hardly any comparative data available
for the other interleukins. The al-microglobulin
inhibits antigen stimulation of lymphocytes. It is a
glycoprotein which in various primates has a
length of 198 amino acids and a molecular mass of
31-32 kDa; in other mammals (mouse, rat,
guinea-pig, horse) and in the chicken, the molecular weight is only 24-26 kDa [1, 190].
Virus infection of almost all vertebrate cells
induces the production and secretion of interferons (IFN). These bind to high-affinity receptors
of other cells and enhance resistance to the virus
by an as yet unknown mechanism. The interferons have immunoregulatory functions in addition to their antiviral role: they stimulate the
cytotoxic activity of T lymphocytes, macrophages
and the so-called natural killer cells, which lyse
foreign and transformed self cells but do not
belong to the T- or B-lymphocyte categories. All
interferons activate the expression of class I
MHC genes and the ~z-microglobulins; one particular type of interferon (IFN-y) also stimulates
the expression of class II MHC genes [136].
Three families of IFN s can be distinguished in
the mammals: the leukocyte IFN or IFN-a, the
fibroblast IFN or IFN-~, and the immune IFN or
IFN-y. IFN-a and IFN-~ are very similar and are
therefore classified as type I; IFN-y is classified
as type II. IFN-a has a molecular weight of
16-27 kDa and in man usually consists of
6.5 Cytokines and Interferons
231
165-166 amino acids. In addition, there is a further type (IFN-w, -aL or -all) in man and some
other mammals with a length of 172 amino acids.
There are 23 IFN-a genes on human chromosome
9, of which 14 can be expressed. Only one of the
14 active genes encodes an IFN with an asparagine that can be glycosylated; the other IFNs are,
in all cases, O-glycosylated. The IFN-a molecules
encoded by the different genes differ in about
20 % of positions. In addition, the heterogeneity
of IFN-a is increased by post-translational cleavage of C-terminal amino acids by partial proteolysis. IFN-a multi-gene families are also found in
the mouse, rat and cow. Pairwise sequence comparisons between these species show agreement
of about 60 % [136].
The IFN-~ gene is also located on human
chromosome 9. The encoded sequence of 166
amino acids shows only about 33 % agreement
with IFN-a2. Nevertheless, IFN-a and -~ compete for the same receptors on target cells. Surprisingly, the activity remains unchanged when the
62-Glu found in all known human, murine and
bovine IFN-a and -~ is exchanged for lysine [191].
Whilst humans, like most mammals, have only
one IFN-~ gene, the lion and the rabbit have two
genes, and cattle, horses and pigs have many.
There are IFN-~-like sequences on other human
chromosomes. However, the so-called IFN-~2
gene is not significantly homologous to IFN-~ and
its product has little antiviral activity; apparently,
it does not belong to the IFN-~ family. Both IFN~ and IFN-a genes are always without introns. In
contrast, the gene for IFN-y on chromosome 12
has three introns. The sequence of 146 amino
acids shows no significant homology to either
IFN-a or -~, and IFN-y binds to its own specific
receptor. The carbohydrate-free chain has a molecular mass of 17.1 kDa, and the native molecular
mass is 20 or 25 kDa, depending on whether only
the 28-Asn or also the 100-Asn is glycosylated
[21].
The three IFN families are found in all mammals. In other vertebrates, proteins similar to
IFN-a and -~ but not to IFN-y have been
detected. The sequence similarity between IFN-a
and IFN-~ indicates that the gene duplication that
separated the two families occurred about
300 million years ago, i.e. before the separation
of the reptiles, birds and mammals. Accordingly,
the fish and amphibians should possess only one
IFN family [136].
cells in cooperation with foreign antigens and IL1; it induces the proliferation of T cells and their
production of y-interferon. IL-2 has so far not
been unambiguously detected in birds and lower
vertebrates and shows large variation in immunological and functional characters amongst the
mammals. Human and bovine pre-IL-2, including
the 20 residues of the signal peptide, have lengths
of 153 and 155 amino acids, respectively; in the
rat, there are 169 amino acids, including a unique
sequence of 12 consecutive glutamines. There is
one N-linked carbohydrate chain in the bovine
IL-2 and two in the human and rat forms. The
sequences of IL-2 agree in these three species in
60-65 % of positions [31]. Interleukin-3 (IL-3) is
mainly produced by antigen-stimulated T cells
and stimulates the formation of all the blood cell
types originating in the stem cells of the bone
marrow. Rat IL-3 differs from the murine form in
46 % of its amino acids and has only a limited
effect on murine bone marrow cells. Surprisingly,
the sequence agreement in the flanking NT regions (90 %) and the four introns (80 %) is greater
than in the exons (76 %) of these species [35].
There are hardly any comparative data available
for the other interleukins. The al-microglobulin
inhibits antigen stimulation of lymphocytes. It is a
glycoprotein which in various primates has a
length of 198 amino acids and a molecular mass of
31-32 kDa; in other mammals (mouse, rat,
guinea-pig, horse) and in the chicken, the molecular weight is only 24-26 kDa [1, 190].
Virus infection of almost all vertebrate cells
induces the production and secretion of interferons (IFN). These bind to high-affinity receptors
of other cells and enhance resistance to the virus
by an as yet unknown mechanism. The interferons have immunoregulatory functions in addition to their antiviral role: they stimulate the
cytotoxic activity of T lymphocytes, macrophages
and the so-called natural killer cells, which lyse
foreign and transformed self cells but do not
belong to the T- or B-lymphocyte categories. All
interferons activate the expression of class I
MHC genes and the ~z-microglobulins; one particular type of interferon (IFN-y) also stimulates
the expression of class II MHC genes [136].
Three families of IFN s can be distinguished in
the mammals: the leukocyte IFN or IFN-a, the
fibroblast IFN or IFN-~, and the immune IFN or
IFN-y. IFN-a and IFN-~ are very similar and are
therefore classified as type I; IFN-y is classified
as type II. IFN-a has a molecular weight of
16-27 kDa and in man usually consists of
6.5 Cytokines and Interferons
231
165-166 amino acids. In addition, there is a further type (IFN-w, -aL or -all) in man and some
other mammals with a length of 172 amino acids.
There are 23 IFN-a genes on human chromosome
9, of which 14 can be expressed. Only one of the
14 active genes encodes an IFN with an asparagine that can be glycosylated; the other IFNs are,
in all cases, O-glycosylated. The IFN-a molecules
encoded by the different genes differ in about
20 % of positions. In addition, the heterogeneity
of IFN-a is increased by post-translational cleavage of C-terminal amino acids by partial proteolysis. IFN-a multi-gene families are also found in
the mouse, rat and cow. Pairwise sequence comparisons between these species show agreement
of about 60 % [136].
The IFN-~ gene is also located on human
chromosome 9. The encoded sequence of 166
amino acids shows only about 33 % agreement
with IFN-a2. Nevertheless, IFN-a and -~ compete for the same receptors on target cells. Surprisingly, the activity remains unchanged when the
62-Glu found in all known human, murine and
bovine IFN-a and -~ is exchanged for lysine [191].
Whilst humans, like most mammals, have only
one IFN-~ gene, the lion and the rabbit have two
genes, and cattle, horses and pigs have many.
There are IFN-~-like sequences on other human
chromosomes. However, the so-called IFN-~2
gene is not significantly homologous to IFN-~ and
its product has little antiviral activity; apparently,
it does not belong to the IFN-~ family. Both IFN~ and IFN-a genes are always without introns. In
contrast, the gene for IFN-y on chromosome 12
has three introns. The sequence of 146 amino
acids shows no significant homology to either
IFN-a or -~, and IFN-y binds to its own specific
receptor. The carbohydrate-free chain has a molecular mass of 17.1 kDa, and the native molecular
mass is 20 or 25 kDa, depending on whether only
the 28-Asn or also the 100-Asn is glycosylated
[21].
The three IFN families are found in all mammals. In other vertebrates, proteins similar to
IFN-a and -~ but not to IFN-y have been
detected. The sequence similarity between IFN-a
and IFN-~ indicates that the gene duplication that
separated the two families occurred about
300 million years ago, i.e. before the separation
of the reptiles, birds and mammals. Accordingly,
the fish and amphibians should possess only one
IFN family [136].