DOI Page / Citation link:
https://doi.org/10.11588/diglit.48120#0116
98
Molecular and Cell Biology of Autoantibodies and Autoimmunity
transcripts, which include precursor tRNAs, 5 S RNA and 7 S RNA. These and
other information elucidating the nature of intracellular antigens argue strongly
for the hypothesis that the autoimmune response is antigen driven and that the
in vivo antigen is a subcellular particle. These subcellular particles are different
in different disease states so that in lupus, one of the forms of subcellular particles
is snRNP while in Sjogrens syndrome the particles are those involved in pol III
transcription. The antigen-driven hypothesis could also explain the polyclonality
of the autoimmune response, since there are many component parts to subcellular
particles including proteins and nucleic acids. In the immune response in
Sjorgrens syndrome, the simultaneous occurrence of antibodies to SS-A/Ro
and SS-B/La, a feature frequently observed in this disease, is explained by the pro-
bable complexing of the SS-A and SS-B particles in vivo and presented to the im-
mune system as such, so that antibody to SS-B is almost always coupled with the
co-expression of antibody to SS-A.
Many investigators have observed that autoantibodies inhibit the function of
their cognate antigens. These include inhibition of precursor mRNA splicing by
antibodies to Sm and U 1-RNP, inhibition of aminoacylation of tRNA by autoan-
tibodies to tRNA synthetases, inhibition of 28 S and 18 S RNA synthesis by au-
toantibody to RNA polymerase 1 and inhibition of in vitro and in vivo DNA
replication by antibody to proliferating cell nuclear antigen (PCNA) or auxiliary
protein of DNA polymerase <5. The meaning of these observations was clarified
in several studies showing that autoantibodies were recognizing unique sites on
the antigens whereas experimentally-induced monoclonal antibodies which were
not inhibitory were recognizing different epitopes. This type of information asso-
ciating recognition of unique epitopes and inhibition of function of the antigen
has been shown for autoantibodies to PCNA, threonyl-tRNA synthetase and the
pyruvate dehydrogenase antigen related to primary biliary cirrhosis.
Base on these considerations, the autoimmune response is very likely to be an-
tigen-driven and the immunogen in vivo appears to be a subcellular particle. The
autoimmune response is directed at various components of the subcellular par-
ticles, but the active or catalytic sites of these particles are often the targets of the
B-cell response.
Molecular and Cell Biology of Autoantibodies and Autoimmunity
transcripts, which include precursor tRNAs, 5 S RNA and 7 S RNA. These and
other information elucidating the nature of intracellular antigens argue strongly
for the hypothesis that the autoimmune response is antigen driven and that the
in vivo antigen is a subcellular particle. These subcellular particles are different
in different disease states so that in lupus, one of the forms of subcellular particles
is snRNP while in Sjogrens syndrome the particles are those involved in pol III
transcription. The antigen-driven hypothesis could also explain the polyclonality
of the autoimmune response, since there are many component parts to subcellular
particles including proteins and nucleic acids. In the immune response in
Sjorgrens syndrome, the simultaneous occurrence of antibodies to SS-A/Ro
and SS-B/La, a feature frequently observed in this disease, is explained by the pro-
bable complexing of the SS-A and SS-B particles in vivo and presented to the im-
mune system as such, so that antibody to SS-B is almost always coupled with the
co-expression of antibody to SS-A.
Many investigators have observed that autoantibodies inhibit the function of
their cognate antigens. These include inhibition of precursor mRNA splicing by
antibodies to Sm and U 1-RNP, inhibition of aminoacylation of tRNA by autoan-
tibodies to tRNA synthetases, inhibition of 28 S and 18 S RNA synthesis by au-
toantibody to RNA polymerase 1 and inhibition of in vitro and in vivo DNA
replication by antibody to proliferating cell nuclear antigen (PCNA) or auxiliary
protein of DNA polymerase <5. The meaning of these observations was clarified
in several studies showing that autoantibodies were recognizing unique sites on
the antigens whereas experimentally-induced monoclonal antibodies which were
not inhibitory were recognizing different epitopes. This type of information asso-
ciating recognition of unique epitopes and inhibition of function of the antigen
has been shown for autoantibodies to PCNA, threonyl-tRNA synthetase and the
pyruvate dehydrogenase antigen related to primary biliary cirrhosis.
Base on these considerations, the autoimmune response is very likely to be an-
tigen-driven and the immunogen in vivo appears to be a subcellular particle. The
autoimmune response is directed at various components of the subcellular par-
ticles, but the active or catalytic sites of these particles are often the targets of the
B-cell response.