Non-random employment of V beta 6 and J beta gene elements and conserved amino acid usage profiles in CDR3 regions of human fetal and adult TCR beta chain rearrangements.

We have studied the usage of V beta 6, D beta, and J beta elements, and the composition of the CDR3 regions of human fetal TCR beta chain rearrangements in a 17 week old fetal thymus and in fetal liver, bone marrow, spleen, and cord blood at 11 and 13 weeks of gestation. These fetal sequences were compared with TCR beta chain rearrangements obtained from post-partum thymus, adult spleen, and adult peripheral blood mononuclear cells. Both fetal and adult TCR V beta 6 rearrangements exhibited a non-random usage of V beta and J beta elements. Up to 90% of the sequences obtained at 11 weeks of gestation used J beta 2 elements, most notably J beta 2.1. In the 13 and 17 week old fetal and in the adult tissues, J beta 1 elements were used in approximately 30% of the rearrangements while, within the J beta 2 rearrangements, J beta 2.1 and J beta 2.7 were used most frequently. Both fetal and adult TCR beta chain CDR3 regions showed non-random usage of amino acids. However, the early fetal repertoire was further limited due to the relative absence of N-regions in up to 60% of the 11 and 13 week old TCR beta chain rearrangements, resulting in smaller antigen binding sites. In fetal and adult TCR beta chain rearrangements the distribution patterns of the length of N-regions and the usage profiles of J beta elements were similar in hematopoietic and peripheral organs, suggesting no apparent preference for particular TCR beta chain rearrangements.(ABSTRACT TRUNCATED AT 250 WORDS)