A novel type of aberrant T cell receptor alpha-chain gene rearrangement. Implications for allelic exclusion and the V-J recombination process

J Immunol. 1990 Jun 1;144(11):4410-9.

Abstract

In the process of analyzing the contribution of nonproductive alpha- and beta-chain gene rearrangements to the allelic exclusion of TCR gene expression, we have found a novel type of aberrant alpha-gene rearrangement. In one alpha-allele of the mouse KB5-C20 T cell clone, a J alpha gene segment has been abutted precisely to a sequence that does not display any homology to known V and D gene segment. The appended sequence originates from within the V alpha locus and is located, in the germ-line, 1 kb upstream of a member of the V alpha 2-gene segment subfamily. No recombination signal sequences have been found contiguous to the recombination point. These observations indicate that in normal T lymphocytes, TCR alpha-genes may be affected by aberrant rearrangements similar to those that predominate in human T cell tumors containing chromosome 14 inversion or translocation. Furthermore, compilation of published data and cloning and sequencing of three additional alpha-alleles has allowed us to examine the status of alpha-loci in nine mouse T cell clones expressing functional alpha beta-heterodimers. Interestingly, in contrast to the situation observed at the beta-locus, only 1 of 18 analyzed alpha-alleles has retained a germ-line unrearranged configuration. In addition, in each T cell clone, alpha-rearrangements on homologous chromosomes were unevenly distributed over the J alpha region and shown to generally involve neighboring J alpha gene segments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Southern
  • Clone Cells
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor*
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • H-2 Antigens / immunology
  • Mice
  • Molecular Sequence Data
  • Ovalbumin / immunology
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombination, Genetic
  • Restriction Mapping
  • T-Lymphocytes / physiology*

Substances

  • H-2 Antigens
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Ovalbumin

Associated data

  • GENBANK/M38098
  • GENBANK/M38099
  • GENBANK/M38100
  • GENBANK/M38101
  • GENBANK/M38102
  • GENBANK/M38103
  • GENBANK/M38104
  • GENBANK/M38105
  • GENBANK/M60999
  • GENBANK/M61123