Cloned CD3+ TcR alpha/beta- Ti gamma A- peripheral blood lymphocytes compared to the Ti gamma A+ counterparts: structural differences of the gamma/delta receptor and functional heterogeneity.
We have assessed the organization of T cell gamma rearranging genes (TRG) in circulating TcR gamma/delta+ lymphocytes which do not express V gamma 9-encoded Ti gamma A+ gamma chain. Following purification of the minor TcR gamma/delta+ Ti gamma A- fraction, cloned cell lines were developed from peripheral blood of 5 individuals. Out of the 26 clones studied, only 3 TcR gamma/delta+ Ti gamma A- cells were found to express a disulfide-linked C1-encoded gamma chain. The remaining 23 Ti gamma A- clones with a C2-encoded nondisulfide-linked receptor were found to display rearrangements of various V genes to J2 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 C gamma 1 encoded chain are produced earlier in T cell ontogeny than the C gamma 2 counterparts. The "non-major histocompatibility complex (MHC) requiring" (i.e., "natural killer-like") cytotoxicity mediated by many TcR gamma/delta+ Ti gamma A- cells appeared to be very low as compared to that of Ti gamma A+ clones. Yet, treatment by the OKT3 monoclonal antibody revealed a strong lytic potential in the Ti gamma A- 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 gamma chains. In an attempt to characterize undefined specificities of Ti gamma A- 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 TcR gamma/delta+ lymphocytes are able, like the TcR alpha/beta+, to recognize and kill target cells through either an MHC-dependent (with involvement of either class I or class II gene products) or a non-MHC-requiring pathway.
Jitsukawa
S
S
Laboratoire d'Immunologie Cellulaire, Département de Biologie Clinique, Institut Gustave-Roussy, Villejuif, France.
Triebel
F
F
Faure
F
F
Miossec
C
C
Hercend
T
T
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D017252:CD3 Complex; D002460:Cell Line; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006684:HLA-DR Antigens / Q000276:immunology; D015809:HLA-DR7 Antigen; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000502:physiology* / Q000648:ultrastructure*; D016692:Receptors, Antigen, T-Cell, gamma-delta
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D006684:HLA-DR Antigens; D015809:HLA-DR7 Antigen; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta