Expression of the T cell gamma gene by a functionally defined human T cell clone. Characterization at DNA, RNA, and cell membrane level.
In the present study we describe one CD2+CD3+ clone termed DS6 which expressed neither CD4 nor CD8 differentiation antigens and failed to react with WT31, a monoclonal antibody directed against the T cell antigen receptor alpha/beta heterodimer. This clone was isolated from peripheral blood T lymphocytes of a patient with a prolonged immunodeficiency after allogeneic bone marrow transplantation. Normal-sized T cell gamma gene transcripts were detected in DS6 by northern analysis, whereas no mature beta or alpha chain mRNA were found. The rearrangement of TCR beta chain genes and T cell gamma genes was analysed. While in DS6, TCR beta chain genes remain in germinal configuration, and a unique pattern of monoallelic T cell gamma gene rearrangement was observed. The rearrangement involves the recently described V gamma 5 segment and the J gamma 1 joining segment, which is located upstream of the C gamma 1 constant region. To determine the molecular structure present on DS6, an immunoprecipitation was performed with monoclonal anti-CD3 antibody and a rabbit antiserum raised against gamma protein. We have observed, in association with the CD3 complex, a 90 kDa structure which under reducing conditions resolves into three subunits of 45, 40 and 37 kDa. We demonstrated that the rabbit anti-gamma serum only immunoprecipitates the two lower bands. The upper band corresponds to a presently undefined T cell receptor chain. Next, we showed the non major histocompatibility complex (MHC)-restricted cytolytic activity exhibited by these CD3+CD4-CD8- cloned T cells and inhibition of the natural killer (NK)-like activity by the anti-CD3 monoclonal antibody. The triggering of CD2 or CD3 molecules increased IL-2 receptor expression on DS6 but failed to induce cell proliferation. This contrasts with recent results obtained with gamma-expressing T cell clones and illustrates the functional heterogeneity of the cells bearing the second T cell receptor.
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018801:CD2 Antigens; D017252:CD3 Complex; D002352:Carrier Proteins / Q000276:immunology; D002462:Cell Membrane / Q000502:physiology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic / Q000276:immunology; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D002352:Carrier Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic