Anti-cardiolipin/beta-2 glycoprotein activities co-exist on human anti-DNA antibody light chains.
We have recently shown that the human anti-DNA antibodies B3 and 33H11 also bind cardiolipin and that the anti-autoantigen activity resides predominantly on their lambda light chains. We now show that the two auto-antibodies possess strong reactivity to the plasma-protein 2-Glycoprotein I (beta2-GPI) also. Utilizing chain shuffling experiments involving an unrelated anti-p185 antibody 4D5 with insignificant reactivity to cardiolipin or to beta2-GPI, we now demonstrate that hybrid Fabs with constituent light chain, but not the heavy chain, of B3 or 33H11, exhibit anti-cardiolipin activity. Furthermore, the constructs possessing the auto-antibody-derived light chain also exhibited significant reactivity to beta2-GPI. The results suggest that anti-DNA, anti-cardiolipin and anti-beta2-GPI activities co-exist on the light chains of the antibodies studied and, importantly, these activities could be transferred to antibody constructs by their light chains alone. Computer-generated models of the three-dimensional structures of the auto-antibodies and their hybrids, suggest predominant interaction of their light chains with domain IV of beta2-GPI.
Kumar
Sanjeev
S
Bloomsbury Rheumatology Unit, Department of Medicine, Centre for Rheumatology, University College London Hospital, Arthur Stanley House, 40-50 Tottenham Street, London W1P 9PG, UK. sanjeev.kumar@antisoma.com
Nagl
Sylvia
S
Kalsi
J K
JK
Ravirajan
C T
CT
Athwal
Dee
D
Latchman
David S
DS
Pearl
Laurence H
LH
Isenberg
David A
DA
D000595:Amino Acid Sequence; D017153:Antibodies, Anticardiolipin / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000974:Antibodies, Antinuclear / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D007147:Immunoglobulin Light Chains; D053482:beta 2-Glycoprotein I