Cloned CD3+TcRα/β−TiγA−peripheral blood lymphocytes compared to the Ti γA+counterparts: structural differences of the γ/δ receptor and functional heterogeneity

摘要

AbstractWe have assessed the organization of T cell γ rearranging genes (TRG) in circulating TcRγ/δ+lymphocytes which do not express Vγ9‐encoded TiγA+γ chain. Following purification of the minor TcRγ/δ+TiγA−fraction, cloned cell lines were developed from peripheral blood of 5 individuals. Out of the 26 clones studied, only 3 TcRγ/δ+TiγA‐ cells were found to express a disulfide‐linked C1‐encoded γ chain. The remaining 23 TiγA−clones with a C2‐encoded nondisulfide‐linked receptor were found to display rearrangements of various V genes to 52 segments on both chromosomes; there was no predominance of a unique rearrangement even though the TRG‐V3 and ‐V4 genes belonging to subgroup I were frequently employed. Together, these findings further strengthen the hypothesis that lymphocytes with a Cγ1 encoded chain are produced earlier in T cell ontogeny than the Cγ2 counterparts. The “non‐major histocompatibility complex (MHC) requiring”(i.e., “natural killer‐like”) cytotoxicity mediated by many TcRγ/δ+TiγA−cells appeared to be very low as compared to that of Ti γA+clones. Yet, treatment by the OKT3 monoclonal antibody revealed a strong lytic potential in the TiγA−lymphocytes with little, if any, natural killer‐like activity. Thus, with respect to the latter function, a substantial heterogeneity is found in cells expressing distinct γ chains. In an attempt to characterize undefined specificities of TiγA−lymphocytes, they were screened against a panel of Epstein‐Barr virus‐transformed B cell lines homozygous for HLA‐DR1 to DR10 determinants; one of the clones was found to recognize DR7. In light of reports from other groups describing class I‐related specificities, it is apparent that TcRγ/δ+lymphocytes are able, like the TcRα/β+, to recognize and kill target cells through either an MHC‐dependent (with involvement