DOI Seite / Zitierlink:
https://doi.org/10.11588/diglit.48120#0120
102 Molecular and Cell Biology of Autoantibodies and Autoimmunity
of the amino acid sequence of this polypeptide segment, several peptides were
synthesized and tested for reactivity by an inhibition assay using sera from pa-
tients with PBC. One peptide, defined by the amino acids (AEIETDKATIGFEV-
QEEGYL), obsorbed serum reactivity to the fusion protein of the original clone.
This peptide contains the lipoic acid binding site KATIGF of the dihydrolipo-
amide acetyltransferase found in the inner mitochondrial membrane. Of par-
ticular interest, inhibition of PDH activity was demonstrated after incubation
with sera from patients with PBC but not from normal volunteers or patients with
chronic active hepatitis (CAH). Such inhibition was abrogated by absorption of
the PBC sera with pRMIT-603. Thus, it appears that for this autoantigen, the
target of the autoantibodies corresponds to a functional site of the dihydrolipo-
amide acetyltransferase. Dihydrolipoamide is a very well-conserved antigen and
the identification of immunoreactive sites provides the opportunity to address the
molecular basis of self-recognition and putative mechanisms of biliary duct
destruction.
Association of Seropositive Rheumatoid Arthritis (RA) with the Third
Hypervariable Region (HVR3) of the HLA-DR /?1-Chain: Functional
Implications for Antigen-Specific and Allogeneic T Cell Recognition
C. M. Weyand, J. J. Goronzy
Div. of Rheum., Dept, of Med., University of Heidelberg, FRG
The genetic predisposition to develop seropositive rheumatoid arthritis (RA)
is inherited within two different alleles, HLA-DR 1 and HLA-DR 4. Sequence
analysis and studies with T cell clones have demonstrated that the association for
RA can be localized to the HLA-DR ^1-chain. The genetic polymorphism of the
HLA-DR /? 1-chain is clustered in three hypervariable regions which might cor-
relate to different functional domains of the HLA-molecule on the cell surface.
We have now used antigen-specific T cell clones generated from patients with RA
and allogeneic T cell clones raised against cells of patients with RA to address
the question which functional properties of the HLA-DR /M-chain are associated
with RA. By the use of alloreactive T cell clones a cluster of T cell epitopes can
be defined which are shared amongst the RA-associated haplotypes HLA-DR 1,
Dw4, Dwl3, Dwl4 and Dwl5. Sequence homologies between the HVR3 of the
RA-associated haplotypes allowed to map the crossreactive T cell epitopes to that
functional region. However, the RA-associated T cell epitopes could not be strict-
of the amino acid sequence of this polypeptide segment, several peptides were
synthesized and tested for reactivity by an inhibition assay using sera from pa-
tients with PBC. One peptide, defined by the amino acids (AEIETDKATIGFEV-
QEEGYL), obsorbed serum reactivity to the fusion protein of the original clone.
This peptide contains the lipoic acid binding site KATIGF of the dihydrolipo-
amide acetyltransferase found in the inner mitochondrial membrane. Of par-
ticular interest, inhibition of PDH activity was demonstrated after incubation
with sera from patients with PBC but not from normal volunteers or patients with
chronic active hepatitis (CAH). Such inhibition was abrogated by absorption of
the PBC sera with pRMIT-603. Thus, it appears that for this autoantigen, the
target of the autoantibodies corresponds to a functional site of the dihydrolipo-
amide acetyltransferase. Dihydrolipoamide is a very well-conserved antigen and
the identification of immunoreactive sites provides the opportunity to address the
molecular basis of self-recognition and putative mechanisms of biliary duct
destruction.
Association of Seropositive Rheumatoid Arthritis (RA) with the Third
Hypervariable Region (HVR3) of the HLA-DR /?1-Chain: Functional
Implications for Antigen-Specific and Allogeneic T Cell Recognition
C. M. Weyand, J. J. Goronzy
Div. of Rheum., Dept, of Med., University of Heidelberg, FRG
The genetic predisposition to develop seropositive rheumatoid arthritis (RA)
is inherited within two different alleles, HLA-DR 1 and HLA-DR 4. Sequence
analysis and studies with T cell clones have demonstrated that the association for
RA can be localized to the HLA-DR ^1-chain. The genetic polymorphism of the
HLA-DR /? 1-chain is clustered in three hypervariable regions which might cor-
relate to different functional domains of the HLA-molecule on the cell surface.
We have now used antigen-specific T cell clones generated from patients with RA
and allogeneic T cell clones raised against cells of patients with RA to address
the question which functional properties of the HLA-DR /M-chain are associated
with RA. By the use of alloreactive T cell clones a cluster of T cell epitopes can
be defined which are shared amongst the RA-associated haplotypes HLA-DR 1,
Dw4, Dwl3, Dwl4 and Dwl5. Sequence homologies between the HVR3 of the
RA-associated haplotypes allowed to map the crossreactive T cell epitopes to that
functional region. However, the RA-associated T cell epitopes could not be strict-