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. 2001 Jan;123(1):1-8.
doi: 10.1046/j.1365-2249.2001.01380.x.

Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of VHCDR3 and residues intrinsic to the heavy chain variable region

R A Mageed  1 , I J Harmer, S L Wynn, S P Moyes, B B Maziak, M Brüggemann, C G MacKworth-Young
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Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of VHCDR3 and residues intrinsic to the heavy chain variable region (VSports注册入口)

R A Mageed et al. Clin Exp Immunol. 2001 Jan.

Abstract

To formulate a 'logic' for how a single immunoglobulin variable region gene generates antibodies with different antigen specificity and polyreactivity, we analysed chimeric antibodies produced in transgenic mice carrying the germ-line human V3-23 gene, multiple diversity (D) and joining (J) gene segments. Hybridomas producing antibodies encoded by the V3-23 gene in combination with different mouse Vkappa genes were obtained by fusion of splenocytes from transgenic mice. All antibodies had human mu-chains and mouse light chains, were multimeric in structure and expressed the human V3-23 gene VSports手机版. Nucleotide sequence analyses of genes encoding the heavy and light chains of 12 antibodies in relation to antigen specificity highlighted the importance of heavy chain variable region CDR3 in determining reactivity with different antigens. However, the results also suggest that non-CDR3 sequences intrinsic to the V3-23 gene itself may be involved in, or determine, the binding of the chimeric antibodies to some of the antigens tested in the current study. .

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Figures

Fig. 2
Fig. 2
Sequences of mouse Vκ genes in the chimeric antibodies described in the study. Codons at selected positions in the FRs and the CDRs are shown for brevity. All other codons not shown are identical to the closest indicated germ-line mouse. Sequences of mouse Vκ genes and Jκ genes are given in bold. The predicted amino acids are given above each nucleotide codon of the top germ-line gene MMVK21A. Predicted amino acid sequences in the remaining germ-line and rearranged genes are indicated only if different from MMVK21A.
Fig. 3
Fig. 3
DH region gene segment rearrangements in the chimeric antibody-producing hybridomas. Sequences are shown aligned to the most closely related germ-line DH sequences. Positions of sequence homology are indicated by a dash. Underlined bases are likely to be from the 3′ non-coding region of the V3–23 gene. Putative P nucleotide additions are indicated by lower case letters. Possible N-additions are given in bold italics.
Fig. 1
Fig. 1
Sequences of V3–23 gene rearrangements in chimeric antibodies described in the study. Numbering is according to Kabat et al. [20]. Codons at selected positions in the FRs and the CDRs are shown for brevity. All other codons not shown are identical to the germ-line V3–23. Sequences of the V3–23 germ-line gene and the JH genes are given in bold. Dashes represent identity. Nucleotide changes leading to amino acid replacements are in uppercase and silent changes are in lowercase letters. The predicted amino acids are given above each nucleotide codon.
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References (V体育平台登录)

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