Invariant or highly conserved TCR alpha are expressed on double-negative (CD3(+)CD4(-)CD8(-)) and CD8(+) T cells

TCR alpha (TCRA) expression was examined in RNA samples from PBMC and isola ted populations of CD4(+), CD8(+), and DN T cells from 15 healthy individua ls. The expressed TCR repertoire was surveyed using spectratype analysis, a technique that displays the distribution of complementarity determining re gion 3 (CDR3) lengths for each TCRAV gene family. The results revealed the presence of unusual populations of double-negative (DN; CD4(-)CD8(-)CD3(+)) T cells that express invariant or conserved TCRAV4A, AV7, AV19, and AV24 c hains. Each of the conserved TCRA families was over-represented in >70% of the individuals studied, and all individuals expressed at least one of the over-represented TCRAV families, Over-represented conserved AV4A or AV7 seq uences were also present in CD8(+) T cells from most donors. The extent of TCRA sequence conservation is unparalleled. TCRAV4A, AV19, and AV24 sequenc es were invariant, although AV4A and AV19 transcripts contained N region ad ditions. TCRAV24 transcripts derived from the direct juxtaposition of V and J gene segments. TCRAV7 sequences showed some diversity in two amino acids encoded at junctions of V and J gene segments. Although derivation of DN T cells with conserved TCRA chains is puzzling, the nide-spread expression o f these unusual cells suggests an important function.