Human T-cell antigen receptor (TCR) 6-chain locus and elements responsible for its deletion are within the TCR a-chain locus

Individual T cells express the CD3 molecule in association with alternative y8 or ad heterodimeric T-cell receptors (TCRs). T-cell precursors and occasional y8-expressing T cells in humans possess an unexpected 2.0-kilobase (kb) mRNA in which a tandemly repeated motif, TEA (T early a), has been spliced to the constant (Ca) region. Long-range pulsed-field gel mapping as well as molecular cloning showed that TEA is located immediately 5' to the most upstreamjoining (J.) segment of the TCR a-chain locus. The TCR 8-chain locus is immediately 5' to TEA, and diversity (Dt,) gene segments, J., CB, and TEA are linked within 35 kb. The human TCR 8 locus conserves a 12/23-base-pair (bp) spacer paradigm in which Jr1 possesses a 12-bp and V;1 a 23-bp spacer, while the Dr segments have a 12 bp-D6-23 bp spacer motif. Considerable TCR 8 diversity can be generated despite the predominant use of one Vs8 and one .1 segment. Two Dr segments, Dsl and Ds2 , are 9 and 13 bp long, are frequently recombined as D81-D82, and reveal exonucleolytic trimming with extensive N-segment addition.