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Characterization of the human Ig heavy chain antigen binding complementarity determining region 3 using a newly
M Margarida Souto-Carneiro1, Nancy S Longo, Daniel E Russ
1Repertoire Analysis Group, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 22, 2004
Summary
Human V(H)DJ(H) rearrangements were analyzed using JOINSOLVER. Productive rearrangements had shorter complementarity determining region 3 (CDR3(H)) due to selection against TdT activity and for shorter D segments.
Area of Science:
- Immunology
- Molecular Biology
- Bioinformatics
Background:
- The human immunoglobulin heavy chain V(H)DJ(H) rearrangement is crucial for adaptive immunity.
- Understanding the factors shaping the complementarity determining region 3 (CDR3(H)) is key to deciphering antibody diversity and function.
Purpose of the Study:
- To analyze human V(H)DJ(H) rearrangements and identify factors influencing CDR3(H) structure.
- To characterize D segment usage and selection biases in productive and nonproductive rearrangements.
Main Methods:
- Development and application of a novel program, JOINSOLVER, for analyzing V(H)DJ(H) rearrangements.
- Statistical analysis of nucleotide lengths, D segment usage, and reading frame selection in 77 nonproductive and 574 productive rearrangements.
Main Results:
- Productive CDR3(H) regions were significantly shorter than nonproductive ones.
- D segment usage was biased by molecular mechanisms and selection, with specific D segments and reading frames favored in the productive repertoire.
- A bias in D segment and J(H) segment pairing was observed in nonproductive rearrangements.
Conclusions:
- JOINSOLVER provides comprehensive insights into the shaping of the human CDR3(H) region.
- Both molecular mechanisms and selection processes significantly influence V(H)DJ(H) rearrangement composition and antibody repertoire diversity.