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Junctional diversity in the absence of N-regions - neonatal T-cell receptor beta-chain junctional sequences are more heterogeneous than neonatal T-cell receptor-gamma-delta or IgH junctions

Academic Article
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Overview

authors

  • Feeney, Ann

publication date

  • 1993

journal

  • Journal of Immunology  Journal

abstract

  • Early in ontogeny, Ig, TCR-alpha beta, and TCR-gamma delta lack N regions. In addition, Ig and TCR-gamma delta junctions preferentially occur at regions of short sequence homology, thus limiting junctional diversity for these neonatal lymphocyte populations. Here, we analyze the extent of heterogeneity in TCR-beta chain junctions made early in ontogeny. DNA and cDNA from fetal/neonatal thymocytes were amplified by polymerase chain reaction, and the V-D and D-J junctions from these randomly generated sequences were analyzed. The D-J junctions were very heterogeneous, and displayed little evidence of homology-directed recombination. The V beta 8-D and V beta 5-D junctions that we analyzed each had a particular junctional sequence that was created at the site of a two-nucleotide homology, but in each case that sequence only comprised 10 to 17% of the total sequences. This junctional heterogeneity of N region lacking TCR-beta chains can be partially explained by a relative paucity of homologies at the appropriate locations near the coding ends, particularly at the D-J junction, but other factors such as the sequence surrounding the homology may also contribute. Thus, TCR-beta chains have extensive junctional heterogeneity early in ontogeny before N regions begin to be added. Since TCR-alpha beta CDR3 plays a major role in binding antigenic peptides, this junctional heterogeneity is likely to be advantageous for establishing a diverse TCR repertoire. We suggest that the sequences of the coding ends of the TCR-alpha beta have been selected through evolution to avoid the restricted junctional diversity resulting from homology-directed recombination.

subject areas

  • Animals
  • Animals, Newborn
  • Base Sequence
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor
  • Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor
  • Immunoglobulin Heavy Chains
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Sequence Homology, Nucleic Acid
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 8397251
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Additional Document Info

start page

  • 3094

end page

  • 3099

volume

  • 151

issue

  • 6

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