DOI Seite / Zitierlink:
https://doi.org/10.11588/diglit.48120#0061
Abstracts
43
The antigenic determinants reacting with anti-RNP autoantibodies are located
on the U 1 RNP-specific proteins 70 K, A and C, while the major immunoreactive
Sm proteins are B', B and D. Antibodies against the common proteins E, F and
G, as well as against the other snRNP-specific proteins including some of the U 5
specific proteins, also occur in some patient sera, but they are much less abun-
dant.
The morphology of purified U1 RNPs and the distribution of the RNP- and
Sm-antigenic proteins at the surface of the U 1 RNP particle has been examined
in the electron microscope by negative staining. U 1 RNP exhibits distinctive
structural features, i.e. two characteristic protuberances 4-7 nm long and
3-4 nm wide that emerge from a central body about 8 nm in diameter. Electron
microscopy of individual U 1 RNP particles gradually depleted of their specific
proteins revealed, that the RNP antigenic proteins 70 K and A are contained in
the two U 1 protuberances, while the round shaped body of the particel represents
the core RNP structure encompassing the Sm proteins. Similar studies have been
performed with the 20 S U 5 RNP particles which shows an overall elongated
shape, about 23 nm long and 10 nm wide.
The antigenic structure of U 1 snRNP has further been studied by immunizing
genetically nonautoimmune mice with isolated U1 RNP particles. The antibody
pattern produced by the mice was found to resemble the anti-RNP and anti-Sm
autoimmune response in SLE patients closely. Not only were the major RNP- and
Sm-antigenic proteins also predominantly immunogenic in the mice but they pro-
duced antibodies against the same regions on the antigenic polypeptides as do pa-
tients during the autoimmune response. This was verified by competitive binding
studies with monoclonal antibodes derived from the mice as well as by mapping
the autoimmunizing B cell epitopes using recombinant DNA approaches. These
data suggest that the human autoantibody response is driven by endogeneous
UsnRNP particles.
Autoantibodies to nucleolar components are a common serological feature of
patients suffering from scleroderma, a collagen vascular autoimmune disease.
While animal models, which spontaneously develop abundant anti-nuclear an-
tibodies, have not yet been described, high titers of such antibodies may be induc-
ed by treating susceptible strains of mice with mercuric chloride. In collaboration
with the group of Dr. E. Gleichmann (Dusseldorf), the major nucleolar au-
toantigen against which the HgCl2-induced IgG autoantibodies from mice of
strain B 10.S are directed, has been identified. It is a protein of apparent molecu-
lar weight of 36 kDa and pl value of about 8.6 which is associated with the
nucleolar snRNA U3, and by these criteria, must be identical with a polypeptide
called fibrillarin. It is striking that scleroderma patients spontaneously produce
autoantibodies against the same U 3 RNP protein. Our results provide a basis to
investigate at the molecular level whether similar immunoregulatory dysfunctions
may lead to the preferential anti-U 3 RNP autoantibody production in the animal
model and in scleroderma patients.
43
The antigenic determinants reacting with anti-RNP autoantibodies are located
on the U 1 RNP-specific proteins 70 K, A and C, while the major immunoreactive
Sm proteins are B', B and D. Antibodies against the common proteins E, F and
G, as well as against the other snRNP-specific proteins including some of the U 5
specific proteins, also occur in some patient sera, but they are much less abun-
dant.
The morphology of purified U1 RNPs and the distribution of the RNP- and
Sm-antigenic proteins at the surface of the U 1 RNP particle has been examined
in the electron microscope by negative staining. U 1 RNP exhibits distinctive
structural features, i.e. two characteristic protuberances 4-7 nm long and
3-4 nm wide that emerge from a central body about 8 nm in diameter. Electron
microscopy of individual U 1 RNP particles gradually depleted of their specific
proteins revealed, that the RNP antigenic proteins 70 K and A are contained in
the two U 1 protuberances, while the round shaped body of the particel represents
the core RNP structure encompassing the Sm proteins. Similar studies have been
performed with the 20 S U 5 RNP particles which shows an overall elongated
shape, about 23 nm long and 10 nm wide.
The antigenic structure of U 1 snRNP has further been studied by immunizing
genetically nonautoimmune mice with isolated U1 RNP particles. The antibody
pattern produced by the mice was found to resemble the anti-RNP and anti-Sm
autoimmune response in SLE patients closely. Not only were the major RNP- and
Sm-antigenic proteins also predominantly immunogenic in the mice but they pro-
duced antibodies against the same regions on the antigenic polypeptides as do pa-
tients during the autoimmune response. This was verified by competitive binding
studies with monoclonal antibodes derived from the mice as well as by mapping
the autoimmunizing B cell epitopes using recombinant DNA approaches. These
data suggest that the human autoantibody response is driven by endogeneous
UsnRNP particles.
Autoantibodies to nucleolar components are a common serological feature of
patients suffering from scleroderma, a collagen vascular autoimmune disease.
While animal models, which spontaneously develop abundant anti-nuclear an-
tibodies, have not yet been described, high titers of such antibodies may be induc-
ed by treating susceptible strains of mice with mercuric chloride. In collaboration
with the group of Dr. E. Gleichmann (Dusseldorf), the major nucleolar au-
toantigen against which the HgCl2-induced IgG autoantibodies from mice of
strain B 10.S are directed, has been identified. It is a protein of apparent molecu-
lar weight of 36 kDa and pl value of about 8.6 which is associated with the
nucleolar snRNA U3, and by these criteria, must be identical with a polypeptide
called fibrillarin. It is striking that scleroderma patients spontaneously produce
autoantibodies against the same U 3 RNP protein. Our results provide a basis to
investigate at the molecular level whether similar immunoregulatory dysfunctions
may lead to the preferential anti-U 3 RNP autoantibody production in the animal
model and in scleroderma patients.