HLA (A*0201) mimicry by anti-idiotypic monoclonal antibodies.
Soluble MHC Ags and anti-Id (anti-anti-MHC) Abs have both been shown to inhibit MHC alloantigen-specific B cell responses in vivo. We hypothesized that some anti-idiotypic Abs function as divalent molecular mimics of soluble HLA alloantigen. To test this idea, we studied two well-defined anti-idiotypic mAbs, T10-505 and T10-938, elicited in syngeneic BALB/c mice by immunization with CRll-351, an HLA-A2,24,28-specific mAb. Each anti-Id induced "Ab-3" Abs in rabbits that cross-reacted with HLA-A2 but not with HLA-B Ags. Furthermore, each anti-Id could bind to and block Ag recognition by Ha5C2.A2, a human homologue of mAb CRll-351. Both anti-Id mAb displayed weak reactivity with the human mAb SN66E3, which recognized an overlapping but distinct determinant of HLA-A2 Ags; neither reacted with human mAb MBW1, which recognized a nonoverlapping HLA-A2 determinant. Amino acid sequence comparison of mAb CRII-351 heavy and light chain variable region complementarity-determining regions (CDRs) with those of mAb Ha5C2.A2 and SN66E3 revealed short regions of homology with both human mAb; a large insert in the light chain CDR1 of mAb SN66E3 distinguished it from both CRll-351 and Ha5C2.A2. The amino acid sequences of mAb T10-505 and T10-938, which differed markedly from each other, revealed no homology to the alpha2 domain sequence of HLA-A*0201 that contains the CRll-351 mAb-defined epitope. We conclude that structurally different anti-Id Abs can mimic a polymorphic conformational epitope of an HLA Ag. In the case of T10-505 and T10-938 mimicry was not based on exact replication of the epitope by the hypervariable loops of the anti-Id mAb.
Burlingham
W J
WJ
Department of Surgery, University of Wisconsin, Madison 53792, USA. burlingham@surgery.wisc.edu
Jankowska-Gan
E
E
DeVito-Haynes
L
L
Fechner
J H
JH
Hogan
K T
KT
Claas
F H
FH
Mulder
A
A
Wang
X
X
Ferrone
S
S
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007108:Immune Tolerance; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D007518:Isoantibodies / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011817:Rabbits; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012995:Solubility
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D015789:HLA-A2 Antigen; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007518:Isoantibodies