scholarly journals Idiotypic self binding of a dominant germline idiotype (T15). Autobody activity is affected by antibody valency.

1987 ◽  
Vol 165 (5) ◽  
pp. 1332-1343 ◽  
Author(s):  
C Y Kang ◽  
H L Cheng ◽  
S Rudikoff ◽  
H Kohler

We have previously described (1-3) an IgM antibody that binds to PC, expresses the T15 idiotype, and binds also to itself or T15 if insolubilized. Because of the simultaneous presence of complementary idiotopes and paratopes this type of antibody has been termed autobody. The self binding involves the antigen-binding site because the F(ab')2 fragment of T15, PC, and no other haptens inhibit the self binding. DNA sequence analysis of 11E7-1 using primer extension cDNA sequencing showed that the variable sequences of H and L chains of 11E7-1 are identical to the germline sequence of the prototype T15 idiotype. Furthermore, monomeric and dimeric T15 IgA were shown to bind to insolubilized T15 and other T15+ antibodies including 11E7-1. Thus, the self-binding activity is an inherent property of the T15 germline sequence. The self binding is highly dependent on the polymeric state of the binding antibody since the IgM pentamer of 11E7-1 is about three fold more effective than the T15 dimer and 50 times more than the T15 monomer. These data suggest that the self-binding activity of a germline-encoded idiotype may play an important role in the biology of its expression, and more specifically, may be responsible for the establishment of its dominant expression.

2021 ◽  
Vol 118 (42) ◽  
pp. e2107249118
Author(s):  
Somanath Kallolimath ◽  
Lin Sun ◽  
Roman Palt ◽  
Karin Stiasny ◽  
Patrick Mayrhofer ◽  
...  

Monoclonal antibodies (mAbs) that efficiently neutralize SARS-CoV-2 have been developed at an unprecedented speed. Notwithstanding, there is a vague understanding of the various Ab functions induced beyond antigen binding by the heavy-chain constant domain. To explore the diverse roles of Abs in SARS-CoV-2 immunity, we expressed a SARS-CoV-2 spike protein (SP) binding mAb (H4) in the four IgG subclasses present in human serum (IgG1-4) using glyco-engineered Nicotiana benthamiana plants. All four subclasses, carrying the identical antigen-binding site, were fully assembled in planta and exhibited a largely homogeneous xylose- and fucose-free glycosylation profile. The Ab variants ligated to the SP with an up to fivefold increased binding activity of IgG3. Furthermore, all H4 subtypes were able to neutralize SARS-CoV-2. However, H4-IgG3 exhibited an up to 50-fold superior neutralization potency compared with the other subclasses. Our data point to a strong protective effect of IgG3 Abs in SARS-CoV-2 infection and suggest that superior neutralization might be a consequence of cross-linking the SP on the viral surface. This should be considered in therapy and vaccine development. In addition, we underscore the versatile use of plants for the rapid expression of complex proteins in emergency cases.


2021 ◽  
Vol 7 (10) ◽  
pp. eabf2403
Author(s):  
Pierre Nottelet ◽  
Laure Bataille ◽  
Geraldine Gourgues ◽  
Robin Anger ◽  
Carole Lartigue ◽  
...  

Mycoplasma immunoglobulin binding (MIB) and mycoplasma immunoglobulin protease (MIP) are surface proteins found in the majority of mycoplasma species, acting sequentially to capture antibodies and cleave off their VH domains. Cryo–electron microscopy structures show how MIB and MIP bind to a Fab fragment in a “hug of death” mechanism. As a result, the orientation of the VL and VH domains is twisted out of alignment, disrupting the antigen binding site. We also show that MIB-MIP has the ability to promote the dissociation of the antibody-antigen complex. This system is functional in cells and protects mycoplasmas from antibody-mediated agglutination. These results highlight the key role of the MIB-MIP system in immunity evasion by mycoplasmas through an unprecedented mechanism, and open exciting perspectives to use these proteins as potential tools in the antibody field.


1986 ◽  
Vol 164 (5) ◽  
pp. 1809-1814 ◽  
Author(s):  
V Agnello ◽  
J L Barnes

Evidence was obtained that both the WA and BLA crossidiotype (XId) groups are conformational antigens requiring both L and H chains and that with heat denaturation the antigens that define the XIds and antigen-binding activity are lost in parallel. In contrast, the primary structure-dependent crossreactive idiotype (CRI), PSL2, which is only weakly detected on native Wa and Bla monoclonal rheumatoid factors (mRFs), became prominently detected on the heated Wa and Bla mRFs. Heat denaturation may provide a simple method for distinguishing Ids determined by conformational antigen from primary structure-dependent Ids. In addition to heat denaturation, some acid conditions commonly used for preparation of RFs were also found to cause marked loss of Id antigen. The finding of PSL2-CRI on Bla mRF indicates that this Id is not unique to the WA XId.


1989 ◽  
Vol 169 (5) ◽  
pp. 1583-1588 ◽  
Author(s):  
K K Gaither ◽  
J B Harley

Idiotypes and antiidiotypes are thought to be important immune regulators and have provided clues for the origin and pathogenicity of autoantibodies. Many lupus and Sjögren's syndrome patients, as well as most neonatal lupus infants with congenital heart block or dermatitis, have antibodies to the ribonucleoprotein Ro/SSA, which is one of a group of RNA-protein autoantigens commonly found in human lupus sera. To characterize the fine specificity of anti-Ro/SSA antibodies, a rabbit antidiotypic serum was prepared against polyclonal affinity purified anti-Ro/SSA F(ab')2. The resulting antiidiotype, anti-Id-Rol, is specific for the F(ab')2 fraction of the anti-Ro/SSA immunogen and its binding to anti-Ro/SSA is inhibited by purified Ro/SSA. These data indicate that the Id-Rol epitope on anti-Ro/SSA is associated with the antigen binding site of these same antibodies. The Id-Rol idiotype was present by ELISA in 3 of 12 additional anti-Ro/SSA preparations from precipitin-positive donor sera and in anti-Ro/SSA from one normal donor with low level antibody. This is the first shared idiotype to be found in the human autoantibodies binding to this RNA-protein antigen. Idiotypic differences between anti-Ro/SSA autoantibodies have the potential to explain the variation in pathologic associations found in individuals who develop this autoantibody specificity.


2003 ◽  
Vol 278 (22) ◽  
pp. 20436-20443 ◽  
Author(s):  
Stephanie Planque ◽  
Hiroaki Taguchi ◽  
Gary Burr ◽  
Gita Bhatia ◽  
Sangeeta Karle ◽  
...  

PEDIATRICS ◽  
1988 ◽  
Vol 81 (2) ◽  
pp. 291-295
Author(s):  
Robert H. Yolken ◽  
Flora Leister ◽  
Siok-Bi Wee ◽  
Robin Miskuff ◽  
Steven Vonderfecht

The prevalence of antibodies to human rotaviruses in commercially available eggs and egg products that are suitable for human consumption was investigated. The yolks of virtually all of the individual eggs and pasteurized pooled egg preparations contain antirotavirus antibodies detectable by means of enzyme immunoassay systems. Also, the eggs and egg preparations are capable of inhibiting the growth of two strains of rotaviruses in tissue culture. Chromatographic studies indicated that the antigen-binding activity is limited largely to the immunoglobulin fractions of the egg yolks. The antibody levels in eggs can be increased by the immunization of hens with purified rotavirus preparations, and the immunoglobulins isolated from the eggs of immunized hens can prevent the development of rotavirus gastroenteritis in experimentally infected animals. Egg preparations might serve as a practical source of antiviral antibodies suitable for consumption by infants and young children.


2008 ◽  
Vol 2 (2) ◽  
Author(s):  
Alan Sondheim

The Internet Text is an extended analysis of the environment of Internet communication, an extended meditation on the psychology and philosophy of Net exchange. As such, it is concerned primarily with virtual or electronic subjectivity – the simultaneous presence and absence of the user, the sorts of libidinal projections that result, the nature of flamewars, and the ontological or epistemological issues that underlie these processes. Internet Text begins with a brief, almost corrosive, account of the subject – an account based on the concepts of Address, Protocol, and Recognition. This section “reduces” virtual subjectivity to packets of information, Internet sputterings, and an ontology of the self based on Otherness – your recognition of me is responsible for my Net-presence. The reduction then begins to break down through a series of further texts detailing the nature of this presence; a nature which is both sexualized/gendered, and absenting, the result of an imaginary site. Eventually, it has become clear that everything revolves around issues of the virtual subject, who is only virtual on the Net, but who has a very real body elsewhere. So Internet Text has evolved more and more in a meditation on this subject – a subject which will perhaps be one of the dominant modes of being within the next millennium. Finally, it should be noted that there are no conclusions to be drawn in Internet Text, no series of protocol statements or declarations creating any sort of ultimate defining or explanatory position. The entire history of philosophy mitigates against this; instead, I side with the Schlegels, with Nietzsche, Bataille, Jabes, and others, for whom the fragment is crucial to an understanding of contemporary life... It is dedicated to Michael Current and Clara Hielo.


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