Rabbit Immunoglobulin Allotypes: Complexities of Their Genetics, Expression, Structural Basis, and Evolution

Mage, Rose G.; Young-Cooper, Glendowlyn O.; Rejnek, J.; Ansari, Aftab Alam; Alexander, Cornelius B.; Appella, E.; Carta-Sorcini, M.; Landucci-Tosi, Simonetta; Tosi, Roberto

doi:10.1101/sqb.1977.041.01.077

Cited by 8 publications

(4 citation statements)

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“…Superimposing the allotype-specific residues upon a three-dimensional model (Fig. 7) of the rabbit Ig VH region demonstrates that the key residues are scattered in several clusters over a wide area of the portion of the VH domain which is exposed to the solvent [8]. Thus, there is an ample structural basis for the gener- ation of multiple allotopes.…”

Section: Discussionmentioning

confidence: 99%

Direct demonstration of multiple V_H allotopes on rabbit Ig molecules: allotope characteristics and Fab arm rotational flexibility revealed by immunoelectron microscopy

Roux¹

1984

Eur J Immunol

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Immune complexes composed of rabbit IgG and Fab fragments of antibody specific for the VH framework allotypes were analyzed by molecular immunoelectron microscopy. In this manner, the number of allotypic epitopes ( allotopes ) and their approximate topological location could be determined. A monoclonal anti-allotype Fab was used to show that relatively fine details of allotope location and orientation are demonstrable with this technique. Each of the three VH allotypes (a1, a2 and a3) was found to express at least two spacially separated allotopes . The locations of the allotopes varied for each of the three allotypes. Some allotopes were observed near the VH-CH1 switch region while others were in close proximity to the complementarity-determining region or were at intermediate positions. In addition to the information concerning allotope topology, the variety of configurations resulting from the interaction of monoclonal antibody Fab with IgG suggest considerable rotational flexibility (twisting) of the Fab arm of IgG about its long axis.

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Section: Discussionmentioning

confidence: 99%

Direct demonstration of multiple V_H allotopes on rabbit Ig molecules: allotope characteristics and Fab arm rotational flexibility revealed by immunoelectron microscopy

Roux¹

1984

Eur J Immunol

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“…The phenotypes used in the analysis of V region genes are a function of the primary amino acid sequence of V region domains, but only occasionally has a phenotype been directly related to primary sequence, as in the case of the VH allotypes of the rabbit [57]. Instead, indirect methods of 'sequencing' have been employed.…”

Section: Region Markers: Structural Correlationsmentioning

confidence: 99%

The genetic control of antibody variable regions in the mouse

Weigert¹,

Riblet²

1978

Springer Semin Immunopathol

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The genetic control of the variable (V) 1 regions of mouse antibodies is being analysed at several levels. The direct chemical analysis of V-region genes is underway [87]; antibody V-genes have been isolated from the D N A of differentiated and undifferentiated mouse cells and are now being sequenced. These studies already provide support for the conclusions based on analysis of amino acid sequences of V-regions and the genetic analysis of V-region genes using markers such as idiotype. In this chapter, we will concentrate on what has been learned from the latter kinds of studies such as the approximate size of VL and V H loci, the organization of VH genes and the relationship of V-region and C-region loci. Our purpose will be to bring to date the information on mouse V regions from a variety of sources using as a basis several recent reviews of this field by Eichmann [27], M~ikel~i and Karjalainen 1-59], Potter [74] and the summaries of the H o m o g e n e o u s Immunoglobulin Workshops [90].V-region genetic studies in the mouse owe their rapid development to two systems: the first of these is the mouse plasmacytoma developed by Michael Potter and co-workers. As Melvin Cohn points out, "The mouse system bears the stamp of Michael Potter who systematically developed the methods for provoking and characterizing mouse myelomas and who established a collection of cell lines which are to this field what the T-phages were to molecular biology" [24]. These plasmacytomas have been the source of the homogeneous antibodies used for ~-To whom offprint requests should be sent 1 Antibody structures will be abbreviated throughout this review as follows: the variable regions (V) o f heavy and light chains, VH and VL, and their constant regions, CH and CL. The structures as they relate to types of antibody subunits are abbreviated as V~c and CK (kappa chain) and VZ (lambda chain), V~c-t, etc.; VH-1, etc. (kappa or heavy chain variable region isotype), CH-y2a, etc. (heavy chain constant region isotype)The abbreviations for the gene or locus controlling these structures are for V-regions: Vh, V~c, and V2, for C regions of light chains, C~c and C2; and for heavy chains, the entire locus is designated Ch and specific genes, Ig-1 to Ig-6 according to ref. [34] 0344-4325/78/0001/0133/$ 7.40

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“…The VHa positive molecules (i.e. displaying motifs of VHa -characteristic determinants) also showed variation which revealed the existence of multiple VHa -related gene fragments (Brezin and Cazenave 1975, Mage et al 1976, van der Loo et al 1977). This was later confirmed by genomic mapping of the rabbit VH region which revealed the existence of over 200 VH elements in the germline (Currier et al, 1988; Gallarda et al, 1985; Ros et al, 2004).…”

Section: Rabbit Preferentially Expresses Ighv1mentioning

confidence: 99%

Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids

et al. 2011

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The rabbit has long been a model for studies of the immune system. Work using rabbits contributed both to the battle against infectious diseases such as rabies and syphilis, and to our knowledge of antibodies' structure, function, and regulated expression. With the description of rabbit Ig allotypes, the discovery of different gene segments encoding immunoglobulins became possible. This challenged the “one gene-one protein” dogma. The observation that rabbit allotypic specificities of the variable regions were present on IgM and IgG molecules also led to the hypothesis of Ig class switching. Rabbit allotypes contributed to the documentation of phenomena such as allelic exclusion and imbalance in production of allelic gene products. During the last 30 years, the rabbit Ig allotypes revealed a number of unique features, setting them apart from mice, humans and other mammals. Here, we review the most relevant findings concerning the rabbit IGHV. Among these are the preferential usage of one VH gene in VDJ rearrangements, the existence of trans-species polymorphism in the IGHV locus revealed by serology and confirmed by sequencing IGHV genes in Lepus, the unusually large genetic distances between allelic lineages and the fact that the antibody repertoire is diversified in this species only after birth. The Whole Genome Sequence of rabbit, plus re-sequencing of additional strains and related genera, will allow further evolutionary investigations of antibody variation. Continued research will help define the roles that genetic, allelic and population diversity at antibody loci may play in host-parasite interactions.

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Rabbit Immunoglobulin Allotypes: Complexities of Their Genetics, Expression, Structural Basis, and Evolution

Cited by 8 publications

References 0 publications

Direct demonstration of multiple V_H allotopes on rabbit Ig molecules: allotope characteristics and Fab arm rotational flexibility revealed by immunoelectron microscopy

Direct demonstration of multiple V_H allotopes on rabbit Ig molecules: allotope characteristics and Fab arm rotational flexibility revealed by immunoelectron microscopy

The genetic control of antibody variable regions in the mouse

Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids

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Rabbit Immunoglobulin Allotypes: Complexities of Their Genetics, Expression, Structural Basis, and Evolution

Cited by 8 publications

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Direct demonstration of multiple VH allotopes on rabbit Ig molecules: allotope characteristics and Fab arm rotational flexibility revealed by immunoelectron microscopy

Direct demonstration of multiple VH allotopes on rabbit Ig molecules: allotope characteristics and Fab arm rotational flexibility revealed by immunoelectron microscopy

The genetic control of antibody variable regions in the mouse

Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids

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Product

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Direct demonstration of multiple V_H allotopes on rabbit Ig molecules: allotope characteristics and Fab arm rotational flexibility revealed by immunoelectron microscopy

Direct demonstration of multiple V_H allotopes on rabbit Ig molecules: allotope characteristics and Fab arm rotational flexibility revealed by immunoelectron microscopy