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Multiple mechanisms participate in the generation of diversity of human H chain CDR3 regions
1Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.
Insights
The third complementarity determining region (CDR3) in human antibodies exhibits vast diversity, potentially generating over 10(14) unique peptides. This study explores the mechanisms driving this extensive diversity in the human B cell repertoire.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- The third complementarity determining region (CDR3) is the most variable part of the antibody-combining site.
- Understanding CDR3 variability is crucial for comprehending the human B cell repertoire's diversity.
Purpose of the Study:
- To investigate the diversity potential of human CDR3 regions.
- To identify mechanisms contributing to CDR3 diversity in the human B cell repertoire.
Main Methods:
- Generation of CDR3-specific cDNA libraries from human tissues across developmental stages.
- Computer analysis of over 500 CDR3 sequences.
Main Results:
- Human CDR3 regions have the potential to generate more than 10(14) distinct peptides.
- Mechanisms of diversity include inversion, D-D fusion, gene conversion, and DIR gene utilization.
Conclusions:
- The human CDR3 region possesses immense potential for generating antibody diversity.
- Specific recombination mechanisms contribute to repertoire diversity and may explain developmental differences.
Abstract:
The area of highest variability in the antibody-combining site is the third complementarity determining region or CDR3. Based on our preliminary observation of the tremendous variability of this region in the human system we have studied the potential of CDR3 regions for generating diversity in the human B cell repertoire. To this end we generated CDR3-specific cDNA libraries from tissues collected at several stages of human development. Detailed computer analysis of more than 500 sequences reveals that human CDR3 region have the potential to generate more than 10(14) different peptides. The mechanisms responsible for this diversity include rearrangement by inversion, D-D fusion, gene conversion and the frequent utilization of the recently described DIR genes. The specific recombination mechanisms which may explain aberrant rearrangements as well as differences between fetal and adult repertoires are discussed in detail.