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.

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. 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.

journal_name

Clin Exp Immunol

authors

Mageed RA,Harmer IJ,Wynn SL,Moyes SP,Maziak BB,Brüggemann M,MacKworth-Young CG

doi

10.1046/j.1365-2249.2001.01380.x

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

1-8

issue

1

eissn

0009-9104

issn

1365-2249

pii

cei1380

journal_volume

123

pub_type

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