We study genes of the rabbit immune system by techniques of molecular biology. We used a restriction fragment length polymorphism (RFLP) of the rabbit T cell receptor beta chain constant region genes (C beta) and an RFLP of rabbit immunoglobulin (Ig) kappa light chains (C kappa) to determine that rabbit C beta and C kappa are not genetically linked as they are in mice, but segregate independently as in man. The C kappa RFLP on the other hand is closely linked to the expression of the K2basl Ig allotype and to a newly discovered RFLP of rabbit V kappa genes. No recombinants have been identified to date. We found evolutionary conservation of both sequence and linkage relationships of gene segments encoding T cell receptor beta chain variable regions. Two of three closely linked rabbit V beta genes have homologs that are closely linked in both mouse and man. A third rabbit V beta gene hybridizes strongly to human DNA. The rabbit probe should identify and allow mapping of a previously unidentified human V beta gene. Like other species, some rabbits have two similar C beta genes but we found that others have three and allotypic forms of both C beta 1 and C beta 2. Stretches of alternating purines and pyrimidines 5' of C beta 1 exon 1, a perfect Chi sequence in exon 1, and Chi with one mismatch in the intron 3' of C beta exon 1, surrounding the allotypic positions, may have contributed to the generation of similar allotypic amino acid sequences in both C beta 1 and C beta 2 of individual rabbits (isoallotypes) by a gene-conversion- like mechanism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000226-07
Application #
3821999
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Hofer, Thomas; Tangkeangsirisin, Wisit; Kennedy, Michael G et al. (2007) Chimeric rabbit/human Fab and IgG specific for members of the Nogo-66 receptor family selected for species cross-reactivity with an improved phage display vector. J Immunol Methods 318:75-87
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Mehr, Ramit; Edelman, Hanna; Sehgal, Devinder et al. (2004) Analysis of mutational lineage trees from sites of primary and secondary Ig gene diversification in rabbits and chickens. J Immunol 172:4790-6
Popkov, Mikhail; Mage, Rose G; Alexander, Cornelius B et al. (2003) Rabbit immune repertoires as sources for therapeutic monoclonal antibodies: the impact of kappa allotype-correlated variation in cysteine content on antibody libraries selected by phage display. J Mol Biol 325:325-35
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Sehgal, Devinder; Obiakor, Harold; Mage, Rose G (2002) Distinct clonal Ig diversification patterns in young appendix compared to antigen-specific splenic clones. J Immunol 168:5424-33
Sehgal, D; Schiaffella, E; Anderson, A O et al. (2000) Generation of heterogeneous rabbit anti-DNP antibodies by gene conversion and hypermutation of rearranged VL and VH genes during clonal expansion of B cells in splenic germinal centers. Eur J Immunol 30:3634-44
Dasso, J F; Obiakor, H; Bach, H et al. (2000) A morphological and immunohistological study of the human and rabbit appendix for comparison with the avian bursa. Dev Comp Immunol 24:797-814

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