摘要:

AbstractExperiments were carried out to determine the antigen specificity of two distinct helper T cells (Th) that act synergistically in adoptive secondaryin vivoanti‐hapten antibody responses. Both Th were present in anti‐Ly‐2 and complement‐treated spleen T cell populations, implying that both Th are Ly‐1+,23−. Adding normal T cells or T cells primed to other carriers to specific carrier‐primed T cells, using a variety of different protocols did not affect the helper activity of the specifically primed Th. Thus, both Th apparently are antigen‐specific. Furthermore, Th primed with one carrier and boosted with that carrier plus hapten linked to a noncross‐ reactive carrier cannot help B cells. However, if a mixture of Ly‐1 T cells from mice primed with two different carriers is transferred along with B cells, and the mice are boosted with hapten coupled to one of the two priming carriers, then giving the other carrier induces a significant increase in antibody production. Thus, only one of the two Th (Th1) requires a hapten‐carrier bridge, while the other does not (Th2). However, both Th 1 and Th2 are clearly antigen‐specific and require stimulation with antigen to exert helper activity. Furthermore, these experiments strongly suggest that Th 2 cannot express helper functionin vivoin the absence of Th 1. These findings, and the absence of Th2‐like cells in agammaglobulinemic mice, were correlated with other studies in which two helper activities have been described. It was concluded thatin vivoresponses require an effective Th 1‐B cell interaction, whereas Th2, if stimulated with antigen, will augment certain portions of the antibody response, such as idiotype or allotype, and thus influence the quality of the

ISSN:0014-2980    

DOI:10.1002/eji.1830100402

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractT and B lymphocyte activity in adoptive secondary antibody responses was assessed by cell titration in mice of the X‐linked immune defective CBA/N strain and mice of their normal partner strain CBA/CaJ. No quantitative differences could be detected in either T or B cell activity in these experiments, in which 2,4‐dinitrophenyl was used as the hapten. Both of the helper T cells detected in such assays were present in both strains. During these experiments, it was found that a subline of CBAN maintained at Yale may have diverged from the CBA/N NIH stock. This was detected by an ability of irradiated mice of the Yale subline to increase the antibody response of B cells from the NIH subline, provided specific helper T cells were also present. This allogeneic effect apparently replaced the activity of one helper T cell, but did not replace the requirement for a carrier‐specific helper T

ISSN:0014-2980    

DOI:10.1002/eji.1830100403

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractC3H/He‐mg mice were immunized with C57 BL/10 (B10) spleen cells and the immune spleen cells were fused with BALB/c myeloma cells (NS1). One of the monoclonal antibodies (H9/25 antibody) produced by the hybrid cells was studied. It reacts with subpopulations of B 10 lymphocytes as well as some lymphoid tumor lines including some of the Abelson virus‐induced leukemias. The antigen recognized by H 9/25 antibody is expressed on lymphocytes from all the B 10 congeneic mice tested as well as some other strains of mice. No linkage between genes coding for the antigen and H‐2 loci was found as judged by its presence on cells of the B 10 strains regardless of H‐2 type and the distribution of the antigen on Bailey recombinant inbred mice. The antigen is expressed on subpopulations of lymph node cells, spleen cells, thymocytes and bone marrow cells. The strain distribution of the H9/25 antigen seems to be identical to that of Ly‐6, Ly‐8 and Ala‐1 antigens. However, the tissue distribution of the antigen recognized by H9/25 antibody, while similar to these alloantigens, is unique and the antigen may be distinct from the other

ISSN:0014-2980    

DOI:10.1002/eji.1830100404

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractNatural cell‐mediated cytotoxicity (NCMC) against K‐562 target cells was explored in patients with various primary immunodeficiencies. (a) NCMC was present in 2 patients lacking detectable B cells. Conversely, NCMC was depressed in 2 patients with severe combined immunodeficiency presenting a normal number of circulating B cells. These data exclude a major role for B cells in NCMC. (b) NCMC was depressed mainly in patients with severe combined immunodeficiency or with defects affecting cellular immunity, which suggests a major role in NCMC for cells of T lineage. (c) Four patients with various clinical features associated with a lack of immune interferon production exhibited a strikingly depressed NCMC. Interferon thus appears as a majorin vivoactivator of natural killer (NK) cell activity. (d) Eight patients exhibiting a depressed NK cell activity had a normal killer (K) cell activity against L1210 cells in the presence of rabbit anti‐L1210 antiserum. These data are consistent with the assumption that NK and K cell activity are mediated through two distinct cellular mecha

ISSN:0014-2980    

DOI:10.1002/eji.1830100405

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractA natural response acting to discriminate between allogeneic and syngeneic lymphocytesin vivois described for normal mice. Eighteen to 24 h after systemic injections of low doses of51Cr‐labeled cells, less radioactivity is found in the lymph nodes after allogeneic transfer. The spleen but not the liver participates in the response. It can be abolished by neonatal induction of transplantation tolerance, is shown to be immunologically specific, and is resistant to irradiation up to 1000 rd, although a radiosensitive phase occurs during recovery from sublethal irradiation. The response is cell‐mediated but depends upon cooperation from a factor present in normal serum. It is thymus‐independent: this clearly distinguishes it from the superficially similar immune response acquired by immunization and aligns it with the class of responses to which the hybrid histocompatibility response and natural killer‐like phenomena belong. Unlike these, however, it is present at birth and directed primarily against H‐2 antigens. It appears to follow the classical transplantation rules in a limited range of strains. Some of the difficulties inherent in this type of study are

ISSN:0014-2980    

DOI:10.1002/eji.1830100406

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractThe immune response of BALB/c mice to phosphorylcholine (PC) is dominated by an antibody bearing the idiotype of the myeloma protein TEPC 15 (MP T15). Anti‐PC antibody of a different idiotype can be elicited in BALB/c mice by neonatal suppression with an anti‐T15 idiotypic antiserum (anti‐Id‐T15).In an attempt to further characterize the immune response to PC, spleen cells of normal and idiotypically suppressed mice have been fused with the myeloma line X63‐Ag8, and hybrid lines secreting anti‐PC antibodies have been isolated. The antibodies were characterized by two‐dimensional gel electrophoresis and their affinity forPneumococcus pneumoniaewas measured. Using both an A/J and a rabbit anti‐Id‐T15 serum, we could show that 4 out of 5 hybridomas obtained from normal BALB/c spleen cells secreted antibodies which, within the limits of the analysis, were idiotypically and structurally indistinguishable from MP T15 (T15+). Hybridomas obtained from suppressed BALB/c mice, on the other hand, secreted anti‐PC antibodies which differed idiotypically from MP T 15: of the six lines, two were negative for T15 idiotopes (T15−), while four showed some cross‐reactivity with the T15 idiotype (T15cr). All six, however, showed structural differences in one or more immunoglobulin chains.Inhibition of anti‐PC plaque‐forming cells induced in neonatally suppressed mice revealed that the idiotypic spectrum of the hybridoma proteins was representative of clones arising under such conditions in BALB/c mice. The majority of the anti‐PC antibodies in idiotypically suppressed mice still bear idiotopes resembling MP T15. Only a minority,

ISSN:0014-2980    

DOI:10.1002/eji.1830100407

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractThe murine repertoire of anti‐phosphorylcholine (PC) antibodies which do not share the TEPC 15 idiotype was analyzed by partial N‐terminal amino acid sequence determination of the variable (V) regions of five homogeneous IgM PC‐specific antibodies, which were produced by cell fusion of TEPC 15‐suppressed BALB/c spleen cells with X63‐Ag8 myeloma cells. The heavy (H) chains of three of them, HPC 16, 35 and 126, expressed an identical N‐terminal sequence (residues 140) to the TEPC 15 and all other PC‐binding myeloma proteins (PCBMP). The other two (HPC 19, 104) belonged to a new VHisotype, tentatively designated VH‐12, not seen in the library of PCBMP nor in any mouse VHregion known so far. The first hypervariable region of HPC 19 and 104 was different from all those known among PCBMP, thus suggesting that the VH‐12isotype is coded for by a separate germ‐line gene. The variable regions of the light chains (VL) displayed all V, isotypes known in PCBMP, with the exception of the V, isotype of TEPC 15. In addition, one PC‐binding hybridoma protein had the light chain isotype of the parental myeloma immunoglobulin. In the hybridoma IgM antibodies, new VH‐VLcombinations not encountered among PCBMP, as well as known VH‐VLpairings of PCBMP, were expressed. The data suggest that a limited number of VHand VLregions scramble to generate the various PC‐specific antibodies. Thus, the diversity of the murine repertoire of anti‐PC antibodies may be explained at least in part by a nongenetic mechanism of V

ISSN:0014-2980    

DOI:10.1002/eji.1830100408

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractPossible involvement of the major glycoprotein (G protein) of vesicular stomatitis virus (VSV), which is expressed on infected cell surfaces, in the virus‐specific and H‐2‐restricted lysis of targets by cytotoxic T lymphocytes (CTL) was sought by examining the effect of monoclonal antibody directed against the G protein of Indiana (VSVInd) or New Jersey (VSVNJ) serotypes. Evidence is presented that hybridoma supernatants containing monoclonal antibody of the IgG class directed against the G protein of VSVNJcould specifically block the lytic activity of primary CTL obtained from BALB/c mice infected with UV‐inactivated VSVNJ, but not VSVIndfor homotypic but not heterotypic VSV‐infected P815 Y cells. Likewise, monoclonal anti‐VSVIndand anti‐G protein antibody proved effective in blocking the lysis mediated by VSVInd‐ but not VSVNJ‐primed CTL against targets infected with VSVInd, but not those infected with VSVNj. The results of blocking assays are consistent with the interpretation that UV‐inactivated VSVNJor VSVIndcould generate, during the primaryin vivoresponse, CTL subsets which were able to distinguish between serologically distinct VSV G proteins and those which were cross‐reactive for both serotypes. Purified G protein derived from either of the 2 VSV serotypes could inin vitroculture trigger the generation of completely serotype‐specific and H‐2‐restricted secondary CTL from nonlytic precursors primedin vivowith homologous VSV serotype. The lytic activity of secondary VSVNJ‐ and VSVInd‐specific CTL could be blocked by incubation of infected targets with monoclonal anti‐VSVNJand anti‐VSVIndG protein antibodies, respectively. The data obtained are taken as suggestive evidence for the specific recognition of VSV G protein expressed on

ISSN:0014-2980    

DOI:10.1002/eji.1830100409

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractThe binding of a complex containing self Ia and antigen (IAC) to T cells was investigated. Poly‐L (Tyr, Glu)‐poly‐DLAla—poly‐LLys [(T, G)‐A—L], bovine serum albumin, ovalbumin or fowl gamma‐globulin were used as antigen. The effect of this complex was investigated in three experimental systems: autoradiographic antigen binding,in vivoimmunization, andin vitroradioactive suicide of helper T cells. Autoradiographic experiments have shown that antigen binding to T cell‐enriched spleen cells is a slow process with a half‐life period of 20 min. It was found that during this time, antigen which can bind to Lyt‐1+T cells with much faster kinetics (half‐life period = 2 min), is liberated from adherent cells. This “processed” antigen was retained by anti‐Ia or lentil lectin affinity columns, and its binding to T cells was restricted by the I‐A subregion of H‐2. IAC was 100 to 1000‐fold more immunogenicin vivothan the same amount of untreated antigen. This immunogenicity could be removed on anti‐Ia columns, and was found to be under similar H‐2 restriction as was its binding to T cells. The functional T cells, to which IAC binds, were identified by radioactive antigen suicide. It was found that the IAC killed syngeneic but not allogeneic, helper T cells. For the binding of processed antigen, helper cells required metabolic energy and a nonspecific soluble factor of adherent cells. These data are interpreted to suggest that H‐2 restriction is directly determined by the interaction of the helper cell receptor with self Ia and foreign antigen. It also appears that the Ia‐containing antigen ma

ISSN:0014-2980    

DOI:10.1002/eji.1830100410

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY

摘要:

AbstractThe antigen‐binding receptor of helper T cells was studied by radioactive antigen‐ caused suicidein vitro. Purified antibodies to immunoglobulin variable regions, obtained from sera of rabbits immunized with isolated VHand VLfragments of mouse myeloma proteins (MOPC 315, XRPC 25), were used to inhibit the binding of radiotoxic antigen. Anti‐VH, but not anti‐Vγ, or anti‐Vχ, inhibited suicide of carrier‐

ISSN:0014-2980    

DOI:10.1002/eji.1830100411

出版商:WILEY‐VCH Verlag GmbH    

年代:1980

数据来源: WILEY