DOI Page / Citation link:
https://doi.org/10.11588/diglit.48120#0064
46 Molecular and Cell Biology of Autoantibodies and Autoimmunity
22 amino acids present on all 3 P proteins, (iii) all sera recognize the C-terminal
11 residues but there is heterogeneity in binding to the C-terminal 7 residues, (iv)
humans sera show similar binding to synthetic peptides composed of the human
or A. salina amino acid sequences, (v) the C-terminal 22 amino acids are also the
immunodominant epitope recognized by MRL/lpr sera.
To determine, whether the epitope recognized by anti-P is functionally impor-
tant, F(ab')2 or IgG containing anti-P activity was added to rabbit reticulocytes
programmed with globin mRNA in vitro or was microinjected into the cytoplasm
of WI 38 cells in culture. In both systems, anti-P, but not control IgG prepara-
tions, completely abolished protein synthesis. It seems probable therefore that the
immunodominant epitope recognized by anti-P plays a critical role in factor-
ribosome interaction.
Finally, to determine what role the antigens play in anti-P production, we
compared the predicted amino acid sequences of the autoantigen in peripheral
blood mononuclear cells from patients with anti-P and normal controls. cDNA
was specifically primed with an oligonucleotide complimentary to the 3'-region
of P2, subcloned into lambda gtll and sequenced. No differences in the
nucleotide sequences of the cDNA encoding the P2 antigen were observed in the
two groups. Although this observation makes a primary sequence abnormality
unlikely, it does not exclude a role for the antigen in autoantibody induction or
perpetuation.
Molecular Identification of the M2 Antigens of
Primary Biliary Cirrhosis
I.R. Mackay1, M.E. Gershwin2, M. J. Rowley1, R. Uibo1, and C.C.A. Bernard3
1 Centre for Molecular Biology and Medicine, Monash University, Clayton, Victoria,
3168, Australia
2 Department of Medicine, University of California at Davis, CA, USA
3 Brain-Behaviour Research Institute, La Trobe University, Bundoora, Victoria, 3982,
Australia
In 1957 the application of a complement fixation test using human tissues led
to primary biliary cirrhosis (PBC) being recognized as an autoimmune disease.
In 1965 this reactivity was specified by immunofluorescence as anti-mitochon-
drial, and subsequently the reactant was localized to the inner mitochondrial
membrane. In 1985 immunoblotting showed that the mitochondrial (M2) antigen
22 amino acids present on all 3 P proteins, (iii) all sera recognize the C-terminal
11 residues but there is heterogeneity in binding to the C-terminal 7 residues, (iv)
humans sera show similar binding to synthetic peptides composed of the human
or A. salina amino acid sequences, (v) the C-terminal 22 amino acids are also the
immunodominant epitope recognized by MRL/lpr sera.
To determine, whether the epitope recognized by anti-P is functionally impor-
tant, F(ab')2 or IgG containing anti-P activity was added to rabbit reticulocytes
programmed with globin mRNA in vitro or was microinjected into the cytoplasm
of WI 38 cells in culture. In both systems, anti-P, but not control IgG prepara-
tions, completely abolished protein synthesis. It seems probable therefore that the
immunodominant epitope recognized by anti-P plays a critical role in factor-
ribosome interaction.
Finally, to determine what role the antigens play in anti-P production, we
compared the predicted amino acid sequences of the autoantigen in peripheral
blood mononuclear cells from patients with anti-P and normal controls. cDNA
was specifically primed with an oligonucleotide complimentary to the 3'-region
of P2, subcloned into lambda gtll and sequenced. No differences in the
nucleotide sequences of the cDNA encoding the P2 antigen were observed in the
two groups. Although this observation makes a primary sequence abnormality
unlikely, it does not exclude a role for the antigen in autoantibody induction or
perpetuation.
Molecular Identification of the M2 Antigens of
Primary Biliary Cirrhosis
I.R. Mackay1, M.E. Gershwin2, M. J. Rowley1, R. Uibo1, and C.C.A. Bernard3
1 Centre for Molecular Biology and Medicine, Monash University, Clayton, Victoria,
3168, Australia
2 Department of Medicine, University of California at Davis, CA, USA
3 Brain-Behaviour Research Institute, La Trobe University, Bundoora, Victoria, 3982,
Australia
In 1957 the application of a complement fixation test using human tissues led
to primary biliary cirrhosis (PBC) being recognized as an autoimmune disease.
In 1965 this reactivity was specified by immunofluorescence as anti-mitochon-
drial, and subsequently the reactant was localized to the inner mitochondrial
membrane. In 1985 immunoblotting showed that the mitochondrial (M2) antigen