Identical V region amino acid sequences and segments of sequences in antibodies of different specificities: Relative contributions of V(H) and V(L) genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites

E. A. Kabat*, Te Wu Tai Te Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

289 Scopus citations

Abstract

By examining a large database of amino acid sequences of antibodies of various specificities, we have found that many antibodies of distinctly different specificities assemble identical V(L) domains with different V(H) domains. In contrast, rarely is the same V(H) domain found in sets of antibodies of different specificities. We identified additional sets of antibodies of different specificities and identical sequences covering amino acid residues V(H) 1 to 94 and V(L) 1 to 95. In addition, there were segments of additional antibodies for which complete sequences were not available, but identities were seen in V(L) CDR1, V(L) CDR2, and V(L) CDR3 up to the V(L)-J(L) junction. The finding that there are many identical V(L) 1 to 95 segments with different V(H) 1 to 94 sequences, and vice versa, raises important questions as to the role of V(H) in influencing the conformation of V(L) and, conversely, the role of V(L) in influencing the conformation of V(H). Evidence is also cited indicating that a single amino acid change may seriously disrupt site structure and in some instances abolish binding. Our findings suggest that it will be important in the future to investigate further conformational effects on antibody structure by using X-ray crystallography, nuclear magnetic resonance spectroscopy, or other methods, to obtain a better understanding of the functions and topography of antibody-combining sites.

Original languageEnglish (US)
Pages (from-to)1709-1719
Number of pages11
JournalJournal of Immunology
Volume147
Issue number5
StatePublished - 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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