Two types of gamma T cell receptors expressed by T cell acute lymphoblastic leukemias

摘要

AbstractCD3+cells, isolated from peripheral blood of two patients with T cell acute lymphoblastic leukemia (T‐ALL), did not react with the monoclonal antibody WT31, which is thought to recognize a framework determinant on the conventional T cell receptor (TcR), consisting of disulfide‐linked α and β chains. The T‐ALL cells of neither patient synthesized TcRα mRNA; the cells of patient DD contained only truncated (D‐J) TcRβ mRNA, while the cells of patient HZ contained truncated as well as mature (V‐D‐J) TcRβ mRNA. The leukemic cells of both patients made TcRγ mRNA. At the cell surface, the T‐ALL cells of patient DD expressed a CD3‐associated disulfide‐linked dimer, which contained the TcRγ protein. On the leukemic cells of patient HZ the TcRγ protein was present as a 41‐44‐kDa CD3‐associated subunit in a noncovalently linked form. The TcRγ genes in the T‐ALL cells of patient DD were rearranged exclusively to the Cγ1 locus, while in the T‐ALL cells of patient HZ both Cγ1 alleles were deleted and rearrangement to the Cγ2 locus had occurred. The Cγ1 gene segment, just like the TcRα and TcRβ gene segments, contains a cysteine codon in its second exon. This cysteine residue is involved in the formation of the interchain disulfide bond. The human Cγ2 gene segment, however, does not contain a cysteine codon in its second exon. The absence of the cysteine residue in Cγ2 encoded TcRγ chains explains the lack of an interchain disulfide bond in the TcR on the T‐ALL cells of patient HZ. The TcR gene configuration, as well as the expression of TcR mRNA and TcR protein as observed in these two leukemias, is consistent with a model for T cell differentiation in which the TcRγ gene rearranges first to the Cγ1 locus prior to or coinciding with D‐J joining of the TcRβ gene, followed by rearrangement