V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice.
The V region sequences of two anti-DNA (A52, D42) and two anti-RNA (D44, D444) autoantibodies, derived from lupus prone NZB/NZW F1 female mice, were determined by mRNA sequencing. The sequences had the following features: 1) there was no clear sequence relationship between anti-DNA and anti-RNA antibodies; 2) there were no major similarities between any of the L chain sequences and each VL gene segment belonged to a different mouse VK subgroup; 3) the H chains of the two anti-RNA antibodies showed closely related sequences of VH gene segments and very similar third complementarity determining regions (CDR3); 4) the H chains of the two anti-DNA antibodies had VH segments belonging to different VH gene families but had a unique and similar combination of D segments and junctional sequences, suggesting a common recognition element for Ag and/or for idiotypic regulation in the H chain CDR3; and 5) the VH gene segment of one anti-DNA antibody (D42) was found to be very similar to the VH gene segment of a CBA mouse hybridoma antibody (6G6) which binds to the environmental Ag phosphocholine. The three-dimensional structure of the Fv-region of the anti-DNA antibody (D42) was modeled by computer and a stretch of poly(dT), ssDNA was docked to a cleft in the antibody combining site, formed by the three H chain CDR and by CDR1 and CDR3 of the L chain. The cleft is characterized by a preponderance of arginine and tyrosine residues, lining both the walls and base of the cleft.
Eilat
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Department of Medicine A, Hadassah University Hospital, Jerusalem, Israel.
Webster
D M
DM
Rees
A R
AR
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics*; D001483:Base Sequence; D001666:Binding Sites, Antibody; D003196:Computer Graphics; D004247:DNA / Q000276:immunology*; D005260:Female; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D008969:Molecular Sequence Data; D012313:RNA / Q000276:immunology*
D000974:Antibodies, Antinuclear; D007135:Immunoglobulin Variable Region; D008565:Membrane Proteins; C488951:Srpr protein, mouse; D012313:RNA; D004247:DNA