Cytotoxic T cells directed against HLA-DR antigens and their surface proteins.

The authors review their recent research involving the generation of cytotoxic T lymphocytes (CTL) directed against HLA-DR antigens. A mouse anti-human xenogeneic system first suggested that HLA-DR antigens could be recognized by CTL. Human allogeneic CTL specific for HLA-DR6 were generated and found to be OKT4+.

Specificity of OKT4+ cytotoxic T lymphocyte clones.

OKT4+, HLA-DR-specific CTL were cloned by limiting dilution, and two clones were evaluated. One clone, B8, specifically recognized DR6 antigens, whereas another cloned, C6, recognized an Ia-like determinant on some DR 3, 5, and 6 target cells. Both clones were OKT3+, OKT4+, and OKT8-, and their cytolysis could be blocked by OKT3 and OKT4, but not OKT8, antibodies.

Generation of long-term human cytolytic cell lines with persistent natural killer activity.

Human cell lines maintained by in vitro stimulation with the HLA-A, B-negative, DR-positive, Epstein Barr virus-transformed, lymphoblastoid cell line Daudi in the presence of conditioned medium demonstrated significant NK activity for over 6 wk in continuous culture. These cells lyse K562 and a broad panel of lymphoblastoid cell lines but do not lyse normal peripheral blood lymphocytes or pokeweed mitogen blasts. They possess the sheep red blood cell receptor but lack other T cell markers (Lyt-3+, OKT3-).

[Nutritional therapy of tumor patients before, during and after radiotherapy with a new promoter system--Nutromat].

Nutrition and metabolism are vital functions just as respiration and cardio-vascular function which influence general well-being, physical and mental capacity, immunocompetence and wound healing. Malnutrition is a high-risk factor and carries a high morbidity and mortality. 30-50% of our patients nowadays are malnourished.

Genetic control of the cytolytic T lymphocyte response to influenza viruses: H-2 genes influence the response to H-2Kb plus virus.

Genetic control of the cytolytic T lymphocyte responses to influenza virus was examined. Mice bearing the H-2b haplotype and F1 hybrid mice derived from C57BL/6 parents failed to recognize H-2Kb plus type A or type B influenza viruses. Congenic mice that shared H-2Kb but had either H-2Dd of H-2Dq genotypes responded in in vitro secondary cultures to H-2Kb plus virus.

Long-term human cytolytic T-cell lines allospecific for HLA-DR6 antigen are OKT4+.

Human allospecific cytotoxic T lymphocyte lines were established by weekly stimulation of peripheral blood lymphocytes with allogeneic Epstein-Barr virus-transformed lymphoblastoid cell lines in the presence of interleukin 2. The cytotoxic T lymphocyte lines were stimulated by either JY (which expresses HLA-A,B and -DR) or Daudi (which expresses HLA-DR but not -A,B antigens). Specificity of the effector cell lines was determined by antibody blocking and by patterns of cytolysis against a panel of target cell lines.

Key for protein coding sequences identification: computer analysis of codon strategy.

The signal qualifying an AUG or GUG as an initiator in mRNAs processed by E. coli ribosomes is not found to be a systematic, literal homology sequence. In contrast, stability analysis reveals that initiators always occur within nucleic acid domains of low stability, for which a high A/U content is observed.

Specificity of the helper T cell for the cytolytic T lymphocyte response to influenza viruses.

We have described a model system in which helper T cells are required to mount a primary antiviral cytolytic T lymphocyte response. The radioresistant helper cell can be found in the spleens of mice that have been immunized subcutaneously with influenza viruses 6-8 d previously. These helper cells appear to be type specific but cross-reactive among the subtypes of influenza A viruses.

[Analysis of the stability and local cooperativity of DNA: proposal of a molecular mechanism for the initiation of the transcription of gene A3 of bacteriophage T7 by the RNA polymerase from E. coli].

RNA polymerase (RNAP) complexed to the A3 promoter of bacteriophage T7 is known to unwind a DNA segment located downstream of the Pribnow box. This finding can be accounted for if it is assumed that the subunit sigma of RNAP unstabilizes three GC base pairs located just upstream of the transcription start. As a consequence, the rate of promoter utilisation might be related to the relative stability of the DNA between the "Pribnow box" and the transcription start.

[Analysis of the stability and local cooperativity of DNA : elements permitting the recognition of promoters by DNA-dependent RNA polymerase].

Analysis of the local stability of promoters processed by E. Coli RNA polymerase shows that they bear a characteristic stability profile: two segments of low stability are located around --35 and --8 bases ahead of the transcription start and are generally bordered by more stable segments. This key profile may act as a recognition signal for both attracting and positioning the RNA polymerase in the promoter site.

Cellular immune responses of mice to influenza virus vaccines.

Parenteral sensitization of mice with equivalent amounts of untreated, gradient-purified or UV-inactivated influenza A/PR/8/34 virus (PR8 virus) results in the stimulation of maximal serum antibody titers, greatest numbers of antibody-forming cells (AFC), and strong virus-specific cytotoxic T lymphocyte (CTL) activity. In contrast, inoculation of formalin-inactivated virus, which induced antibody titers of equivalent magnitude, did not elicit a measurable primary CTL response nor prime for a secondary response. However, in mice previously exposed to untreated virus, challenge with formalin-inactivated virus evoked a secondary CTL response.

[Use of the degeneracy of the genetic code by selective pressure to cut up genes of procaryote genomes].

The DNA sequences of three bacteriophages are analysed in order to localise those parts coding for a protein. A weak stability on the DNA molecule allows us to characterize the beginning and the end of genes. A survey of the codons used shows that the cause for this weak stability is the systematic use of A-T bases in third position, which is made possible by the degeneracy of the genetic code.

Development and characterization of allospecific long-term human cytolytic T-cell lines.

Two long-term human cytolytic T lymphocyte (CTL) lines (VE and JR), whose cytolytic activity was dependent upon both irradiated JY cells (the stimulating alloantigen) and T-cell growth factor, were established. These lines were monitored in culture for 6-8 months. Both lines were specific for HLA-A or B antigens or both and the JR line was allospecific for HLA-B7.

Influenza type A virus M protein expression on infected cells is responsible for cross-reactive recognition by cytotoxic thymus-derived lymphocytes.

M protein of influenza A virus was detected with rabbit antiserum by both indirect immunofluorescence and by antibody plus complement-mediated cytolysis on the cell surfaces of both productively and nonproductively infected cells. In contrast, antiserum to nucleoprotein failed to react with unfixed infected cells, but did bind to fixed infected cells, especially in the perinuclear area. Incorporation of antiserum to M protein in a T-cell-mediated cytotoxicity assay produced almost complete abrogation of lysis of H-2-compatible cells infected with an influenza A virus of a subtype which differed from that used to elicit the cytotoxic T cells.

[Action and teleaction of specific ligands on DNA: a quantitative study with Azbel's model and an application to the regulatory mechanism of the lac operon].

Assuming that the action of specific ligands is transferred to DNA via the bases in close contact with the ligand, which are stabilized (or destablized) in this process, the local and more distant action of the ligand on DNA can be evaluated quantitatively with the aid of Azbel's model. An application to the system regulating the E. coli lac operon is presented.

[Malignant melanomas of fingers and toes (author's transl)].

From 1968 to 1978 more than 500 patients suffering from histologically verified malignant melanoma were seen. Only in 12 cases (appr. 2%) the tumour was situated on the tip of the fingers and toes.