Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used synthetic peptides duplicating the structures of a human lambda light chain (Mcg), and a human T-cell receptor (Tcr) alpha and a Tcr beta chain predicted from gene sequence to determine the presence and loci of activity of natural human autoantibodies directed against these antigen recognition molecules. We report that normal individuals and patients suffering from autoimmune diseases have antibodies directed against regions of lambda light chains and Tcr beta chains corresponding to the first complementarity determining region and the third framework region of the variable domain and to constant region determinants. The levels of IgM natural antibodies particularly against the CDR1 peptides tend to be higher in RA patients than in normals or SLE patients. Although polyclonal IgG immunoglobulins from healthy individuals did not show detectable reactivity to Tcr alpha peptides, such reactivity was found in the IgM immunoglobulins of RA patients, thereby showing that Tcr alpha peptides can be autoantigenic in man. The levels of IgM autoantibodies to V beta CDR1 peptides tend to decrease with age. By contrast, there was a marked increase in IgG natural autoantibodies to certain CDR1 sequences with advancing age. We suggest that the natural antibodies to defined regions of immunoglobulins and T-cell receptors are part of a physiological network for the regulation of the immune response.
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PMID:Naturally occurring human autoantibodies to defined T-cell receptor and light chain peptides. 797 28

The 8.12 idiotype is expressed in elevated titer in the serum of patients with systemic lupus erythematosus and is a marker for a subpopulation of anti-DNA antibodies that possess a V(lambda)II encoded light chain. This study utilized a eukaryotic expression system to identify the structural basis for expression of this idiotype. Reversion of the 8.12+ DSC light chain to the hslv215.23/DPL11 germline gene reveals that the 8.12 idiotype is encoded in the germline. The 8.12+ DSC and the 8.12 AS17 light chains, both belonging to the V(lambda)II family, were subjected to site directed mutagenesis, to localize amino acids important for expression of the 8.12 idiotype. Point mutations were performed in CDR1, CDR2, FR3 and CDR3, in positions where the 8.12+ DSC differs from the 8.12-AS17. Amino acids in CDR1 and the CDR2 proximal region of FR3, but not the J proximal region of CDR3, play a crucial role in 8.12 reactivity. The 3-D structure of Mcg, a human IgG1, with which DSC shares a sequence homology of 92.3% has been examined to visualize the effect of each of the mutations and to identify the surface on DSC that comprises the idiotype.
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PMID:Molecular mapping of the 8.12 SLE-associated idiotype specificity at the single amino acid level. 912 62