Human delta T cell receptor: rearrangement, deletion, and translocation

Individual T cells express the CD3 molecule in association with alternative gamma delta or alpha beta heterodimeric T cell receptors (TCR). The delta TCR, used in one type of T cell is located within the alpha TCR gene used in quite another cell. T cell precursors and occasional gamma delta T cells in humans possess an unexpected 2.0 Kb mRNA in which a tandemly repeated motif, T early alpha (TEA), has been spliced to the constant (C alpha) region. Long range pulse field gel mapping as well as molecular cloning reveal that TEA is located immediately 5' to the most upstream joining (J alpha) segments of the alpha TCR locus. The human delta TCR locus is immediately 5' to TEA and diversity (D delta 1 +2), J delta 1 +2, C delta, and TEA are linked within 35 Kb. The human delta TCR locus conserves a 12/23 bp spacer paradigm and D delta 1 and D delta 2 are frequently recombined as D delta 1/D delta 2, and reveal exonucleolytic trimming with extensive "N" segment addition. Thus, despite the predominant use of one V delta and J delta segment considerable delta diversity is generated. T cell acute lymphoblastic leukemias (ALL) represent clonal expansions of maturationally arrested cells at specific stages of thymic ontogeny. The gamma delta T-ALLs display allelic exclusion for the delta TCR. Moreover, pre T cells within this group indicate that delta TCR rearrangement can occur prior to the activation of gamma, beta, and alpha loci.(ABSTRACT TRUNCATED AT 250 WORDS)