We have measured the relative levels of transcripts for 15 of the 22 known V(β) gene segments. The level of transcripts for the highest and lowest expressed V)β gene segment differed by >20-fold in the thymus and an even larger difference was observed in the periphery. The levels of expressions were unrelated to the order of the V(β) genes on the chromosome. For most of the V(β) gene segments, the relative transcript levels were the same in the thymus and periphery, suggesting that thymic selection in general does not act solely upon the V(β) gene segment. One V(β) gene segment in the BALB and B10 mice strains was an exception to this rule. V(β)5.2 expression in the periphery of BALB and B10 mice inversely correlated with the expression of the MHC class II molecule I-E. Five V(β) gene segments had reduced transcript levels in the periphery of Mls-1a mice compared with their thymic levels or to the levels found in Mls-1b mice. The peripheral level of V(β)3 transcripts vary with MHC and Mls-2 haplotypes. The observation that certain V(β) transcript levels are reduced in the periphery when compared with the thymus favors the hypothesis that self tolerance at the T cell level results in the elimination of self-reactive T cells, rather than paralysis by a block at some post-transcriptional step. Finally, the wide variability of V(β) gene segment expression in the thymus suggests mechanisms exist to import an early bias to the repertoire. Whether this bias results from differential V(β) segment rearrangement rates, differential V(β) expression rates, or events occurring after TCR-α/β expression on immature/nonmature thymocyte cell surfaces is yet to be determined.
ASJC Scopus subject areas
- Immunology and Allergy