Structural aspects of recognition motifs contributing to autoimmune responses.
Sequence analysis of autoimmune-associated antibodies has suggested a structural relatedness between genes used to encode autoantibodies and those encoding unrelated antibodies without autoreactive specificities. Subsequently, the basis for cross-reactive idiotypes across germ-line lineages, as well as conserved interspecies cross-reactivities of autoantigens among serologically similar antibodies, may result from evolutionary duplication of particular types of recognition motifs. As a first step toward elucidating structural recognition principles underlying possible cross-reactive epitopes involved in autoimmune pathologies, structural features of selected motifs associated with native ligand binding are examined for their inherent occurrence in antibody and T-cell receptor repertoires. This analysis considers the putative recognition features representative of common motif subsets shared with loop structures in CDR2 and FR3 regions of antibodies such as charge-2x-charge-x-charge or hydrogen bond donor (acceptor)-2x-charge-x-hydrogen bond donor (acceptor) type motifs, where x is any residue that can participate in maintaining a loop conformation. Such tracts encoded in the CRD2 and FR3 regions of heavy chains of antibodies and T-cell receptors (TCRs) associated with autoimmune dysfunction, with non-autoreactive antibodies, and with native host proteins. Such evolutionarily conserved motifs may be targets for complementary interactions involving autoantibodies and receptors.
Kieber-Emmons
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Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000737:chemistry / Q000235:genetics; D001323:Autoantibodies / Q000737:chemistry / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics*; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D015394:Molecular Structure
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D000939:Epitopes