Relationship of VH and VL genes encoding three idiotypic families of anti-p-azobenzenearsonate antibodies.

Robbins, Paul F.; Rosen, Edward M.; Haba, Seiji; Nisonoff, Alfred

doi:10.1073/pnas.83.4.1050

Cited by 18 publications

(16 citation statements)

References 28 publications

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“…The primary hybridomas express the VHId cR segment in association with a diverse collection of D and JH segments. Most of these gene segment combinations are similar to those previously observed (1,13) to be expressed by primary hybridomas isolated from the Ars-KLH response . All of the primary Ars-Bruc hybridomas express the VHIdcR gene segment in unmutated form.…”

Section: -supporting

confidence: 66%

“…Molecular analyses of murine humoral immune responses have been largely limited to responses induced by soluble proteins, polysaccharides, and hapten conjugates thereof (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) . However, in nature the mouse rarely encounters an antigenic structure in association with such chemically simple forms, but rather in association with a viral particle, bacterium, or parasite .…”

mentioning

confidence: 99%

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Influence of the macromolecular form of a B cell epitope on the expression of antibody variable and constant region structure.

Fish¹,

Manser²

1987

The Journal of Experimental Medicine

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We investigated the influence of the macromolecular form of an epitope on the structure of antibody variable and constant regions expressed by the B cell population participating in an immune response to that epitope. Hybridomas were constructed from strain A/J mice undergoing either primary or secondary immune responses to p-azophenylarsonate conjugated to Brucella abortus (Ars-Bruc). We determined the sequences of the V genes expressed by hybridomas selected on the basis of expression of a single VH gene segment known to encode a large family of anti-Ars antibodies. These sequences were compared with the sequences of V genes expressed by a previously characterized panel of hybridomas isolated in the same way during the primary and secondary responses of A/J mice to Ars-KLH. The repertoire of Ars-specific V domains expressed among primary and secondary hybridomas elicited with these two forms of Ars were similar, as were the differences between primary and secondary V region somatic mutational alteration and affinity for Ars. In contrast, predominant expression of IgG2 anti-Ars antibodies was elicited in the secondary Ars-Bruc response, whereas secondary anti-Ars antibodies elicited with Ars-KLH are predominantly IgG1. Thus, differences in the macromolecular form of Ars clearly influence the isotypic profile of the anti-Ars response, but the expression, diversification, and selection of V domains elicited with this hapten are not greatly affected by such differences. Our results suggest that while isotype regulation is highly perceptive of the macromolecular form of a B cell epitope, V region regulation is primarily influenced by the molecular structure of that epitope.

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Section: -supporting

confidence: 66%

mentioning

confidence: 99%

Influence of the macromolecular form of a B cell epitope on the expression of antibody variable and constant region structure.

Fish¹,

Manser²

1987

The Journal of Experimental Medicine

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“…Electron density features in VL positions 31,55, and 107 correspond reasonably well with the amino acid sequence encoded by the VK10-Ars-A germ-line gene that encodes the VL region of CRI' antibodies and to the JKl germ-line sequence (Fig. 2).…”

mentioning

confidence: 67%

Three-dimensional structure of Fab R19.9, a monoclonal murine antibody specific for the p-azobenzenearsonate group.

Lascombe

Alzari

Boulot

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The crystal structure of Fab R19.9, derived from an anti-p-azobenzenearsonate monoclonal antibody, has been determined and refined to 2.8-A resolution by x-ray crystallographic techniques. Monoclonal antibody R19.9 (IgG2bK) shares some idiotopes with a major idiotype (CRIA) associated with A/J anti-p-azobenzenearsonate antibodies.The amino acid sequences of the variable (V) parts of the heavy (VH) and light (VL) polypeptide chains of monoclonal antibody R19.9 were determined through nucleotide sequencing of their mRNAs. The VL region is very similar to that of CRIA-positive anti-p-azobenzenearsonate antibodies as is VH, except for its third complementarity-determining region, which is three amino acids longer; it makes a loop, unique to R19.9, that protrudes into the solvent. A large number of tyrosine residues in the complementarity-determining region of VH and VL, with their side chains pointing towards the solvent, may have an important function in antigen binding. Murine antibodies to model antigens have provided valuable experimental systems to study the molecular bases of the specificity, diversity, and genetic control of immune responses. The hapten, p-azobenzenearsonate (Ar), has been used in several laboratories as a suitable probe for such studies (1-5), which have been facilitated by the presence of an intrastrain cross-reactive idiotype, designated CRIA, among the anti-Ar antibodies of A/J mice or ofclosely related strains. The expression of CRIA is linked to genetic loci encoding heavy (H) chains (6) and light (L) chains (7). On the average, about half of the anti-Ar antibodies induced by keyhole limpet hemocyanin-Ar in A/J mice share this idiotype. The variable (V) regions, VH and VL, of CRIA antibodies appear to be encoded by single germ-line genes (8,9), and the diversity (D) region is encoded by a variant of the DFL16.1 gene (10). CRIA molecules also utilize the VK10, K chain joining (J) 1, and, almost invariably, JH2 gene segments (4, 5, 11). Idiotypeexpressing antibodies from hyperimmunized mice display somatic variants ofamino acid sequences in each ofthese gene segments (4, 5, 12), whereas the antibodies from an early primary response reflect few if any mutations (5). The VH region appears to be somewhat more susceptible to somatic variation than VL (4). A disproportionate number of mutations in VH and VL occurs in their complementarity-determining regions (CDR); this probably reflects selection by antigen of variants with higher affinity (5).Among the serum anti-Ar antibodies of immunized A/J mice are molecules that carry some but not all ofthe idiotopes associated with CRIA (13,14). Such antibodies are bound by anti-CRIA antibodies, but they are unable to completely displace labeled CRI+ antibodies from such anti-idiotype antibodies. Antibodies of this type were designated "minor idiotypes" (13,14). The subject of the present investigation, monoclonal antibody (mAb) R19.9 (IgG2bK), has these serological properties and is thus a member of a minor idiotypic anti-Ar family. The ...

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“…21), SM1.5 (IgMK; ref. 22), and SA131 (IgAK; this paper). Keyhole limpet hemocyanin (KLH) was obtained from Calbiochem.…”

Section: Methodsmentioning

confidence: 99%

Induction of high titers of anti-IgE by immunization of inbred mice with syngeneic IgE.

Haba¹,

Nisonoff²

1987

Proc. Natl. Acad. Sci. U.S.A.

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Relationship of VH and VL genes encoding three idiotypic families of anti-p-azobenzenearsonate antibodies.

Cited by 18 publications

References 28 publications

Influence of the macromolecular form of a B cell epitope on the expression of antibody variable and constant region structure.

Influence of the macromolecular form of a B cell epitope on the expression of antibody variable and constant region structure.

Three-dimensional structure of Fab R19.9, a monoclonal murine antibody specific for the p-azobenzenearsonate group.

Induction of high titers of anti-IgE by immunization of inbred mice with syngeneic IgE.

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