SEARCH · PubMed Health

Results for “Antigenic Modulation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed1987

CD5 antibodies increase intracellular ionized calcium concentration in T cells.

The binding of a variety of monoclonal antibodies to the CD5 (T, gp67) pan T cell differentiation antigen has been shown to potentiate T cell proliferation. In this paper we show that CD5 monoclonal antibodies cause increased intracellular free calcium concentration ([Ca2+]i) in T cells. An increase in [Ca2+]i occurred within 1 min in indo-1-loaded PBMC after the addition of CD5 monoclonal antibodies and cross-linking with a second step anti-mouse kappa light chain antibody. Cross-linking of CD5 was effective when done directly on the cell surface or by the administration of preformed soluble complexes that contained CD5 antibodies. Calcium mobilization induced by suboptimal concentrations of CD3 antibodies was specifically augmented and sustained by CD5 antibodies, although the enhancement was modest in magnitude. When cell surface phenotype was correlated with calcium mobilization, it was found that the CD5 response was restricted to CD5+/CD3+ cells, and that approximately 90% of CD5+ cells had responded. CD5-induced calcium mobilization was found to differ from CD3 stimulation in that EGTA entirely ablated the CD5 response, whereas the CD3 response was resistant to EGTA, indicating that the CD5-induced increased [Ca2+]i is derived primarily or entirely from extracellular calcium. CD5-stimulated calcium mobilization also differed from CD3 in that the CD5 response was inhibited by pretreatment with phorbol myristate acetate, whereas the CD3 response was not, suggesting that depletion of protein kinase C causes an uncoupling of signal transduction between CD5 and calcium channels. Finally, experiments were done with T cells after antigenic modulation of the CD3 or CD5 molecules. Unexpectedly, both the CD5 and the CD3 responses were ablated on CD3-modulated cells, whereas only the CD5 response was ablated on CD5-modulated cells. In addition, several Cd5+/CD3- T cell leukemia lines also failed to respond to CD5 stimulation, providing further evidence which indicates that the CD5 response depends on the cell surface expression of CD3 or a CD3-associated structure. These findings suggest that one mechanism for CD5-induced augmentation of mitogen-stimulated T cell proliferation involves increased [Ca2+]i which is distinct from but interdependent with that induced by stimulation of the CD3 molecule.

Antigen-Antibody Reactions↗

PubMed1989

Identification of pre-T cells in human peripheral blood. Extrathymic differentiation of CD7+CD3- cells into CD3+ gamma/delta+ or alpha/beta+ T cells.

CD7+CD3- cells purified (greater than 99.99%) by FACS from the peripheral blood of healthy adults include precursors for mature T cells that have the capacity to differentiate into TCR-1+ or TCR-2+ CD3+ cells. Extrathymic differentiation was demonstrable from all eight healthy donors in the presence of a high concentration of IL-2, mitogenic levels of PHA, and irradiated blood mononuclear feeder cells, after a lag of approximately 40 d in vitro. The extrathymic T (ET) cells were predominantly TCR-1+, although TCR-2+ cells were also derived. ET TCR-1+ cells were CD4-CD8-, CD4-CD8DIM+, and CD4+CD8-, and were distinguished from natural T TCR-2+ cells by a variety of cell surface markers. The ET cells had phenotypes generally displayed by normal mature T cells, although the CD5DIM+ on ET cells was more typical of thymocytes. Acquisition of CD3 on purified CD7+CD3- cells was not due to antigenic modulation or growth of contaminants, and ET cells could be demonstrated at the clonal level. Studies in athymic mice and bone marrow recipients support the view that extrathymic maturation does occur in vivo. Whether the CD7+CD3- cell population was unexposed to the thymus, or exposed but not processed, is unknown. In any case, unusual or "forbidden" autoreactive specificities are predicted since ET cells differentiate without thymic selection of the TCR.

Antigens, CD7↗

PubMed1976

Role of immune mechanisms in metastatic patterns of hemopoietic tumors in rats.

Two hemopoietic tumors induced in rats by Gross leukemia virus and dimethylbenz(a)anthracene, respectively, display distinctive and consistent patterns of metastases, the former in the thymus and lymph nodes, the latter in the liver and spleen. To investigate the role of circulatory anatomy in the localization of metastases, 51Cr-labeled cells were injected i.v., and their distribution was followed at various intervals. To explore the influence of immune mechanisms, Gross leukemia virus- and dimethylbenza(a)anthracene-induced leukemic cells as well as a line of antigenically modulated cells were administered to newborn, X-irradiated, and immunologically unresponsive recipients. The circulation of tumor cells through various organs was indiscriminate. The immune response of the host was operative in limiting the local and metastatic tumor growth but not in determining the site of secondary tumors. The conclusion of these experiments was that the selective organ distribution of tumor metastases was solely dependent on intrinsic cellular properties.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Humanized IgG1 and IgG4 anti-CD4 monoclonal antibodies: effects on lymphocytes in the blood, lymph nodes, and renal allografts in cynomolgus monkeys.

BACKGROUND: Optimizing therapeutic monoclonal antibody (mAb) depends on the incorporation of the necessary effector functions and the development of hypoantigenic "humanized" antibodies by genetic engineering, which then need to be tested in appropriate preclinical trials. METHODS: Constructs of humanized OKT4A containing the complementarity-determining region (CDR) of murine OKT4A and the framework and constant regions of human light (kappa) and heavy chains (IgG1 and IgG4) were prepared and tested in cynomolgus monkeys who received a renal allograft. A prophylactic course of CDR-OKT4A/human (h) IgG1 or CDR-OKT4A/ hIgG4, either as high-dose single bolus (10 mg/kg) or as low-dose multiple infusion (1 mg/kg for 12 days) was given, and the effects on graft survival, immunohistology, circulating cells, and lymph node cells were assessed. RESULTS: The IgG1 isotype induced coating of T cells, modulation of surface CD4 molecules, and profound depletion of CD4+ lymphocytes in peripheral blood, which persisted as long as the animals were followed (up to 7 weeks). The IgG4 isotype induced only cell coating without cell clearance or modulation. In lymph nodes, coating of lymphocytes (approximately 60%) was seen with both isotypes in the earliest sample (6 hr). After 2 days, significant depletion of lymph node CD4 cells was evident, with a decrease in the CD4 to CD8 ratio in the IgG1-treated group; no depletion occurred in the IgG4 group. The emigration of CD4+ cells into the allograft was significantly delayed in the CDR-OKT4A/hIgG1-treated animals when compared with the CDR-OKT4A/hIgG4 group as judged by immunocytochemistry (23.8+/-13.2 days vs. 7.4+/-1.5 days, P<0.001) or interleukin-2-promoted T-cell outgrowth from allograft biopsies (22.2+/-11.0 days vs. 6.3+/-0.5 days, P<0.01). CONCLUSIONS: This study demonstrates that the in vivo effects of CDR-grafted OKT4A are dependent on its isotype. The depleting mAb CDR-OKT4A/hIgG1 significantly delays the entry of CD4+ cells into the graft, inhibiting the early phase of rejection. However, graft rejection occurs when CD4+ cells eventually infiltrate the graft, even in the presence of depressed levels of circulating CD4+ cells. Both isotypes demonstrated therapeutic efficacy: graft survival was prolonged over controls. In the case of CDR-OKT4A/hIgG4, neither lymphocyte depletion, antigenic modulation, nor prevention of infiltration is necessary for a beneficial effect, which indicates that this mAb blocks CD4 function or renders the CD4+ cell less responsive. The lack of depletion is a feature of potential clinical advantage in minimizing the risk of excessive immunosuppression.

Animals↗

PubMed1994

Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice.

Anti-CD3 monoclonal antibodies suppress immune responses by transient T-cell depletion and antigenic modulation of the CD3/T-cell receptor complex. Anti-CD3 treatment of adult nonobese diabetic (NOD) mice, a spontaneous model of T-cell-mediated autoimmune insulin-dependent diabetes mellitus, significantly inhibits the autoimmune process. Short-term low-dose anti-CD3 treatment (5 micrograms/day i.v. for 5 consecutive days) prevented the occurrence of an accelerated form of the disease induced by cyclophosphamide. More unexpectedly, when applied to adult NOD females within 7 days of the onset of full-blown diabetes, the same anti-CD3 regimen induced a complete remission of overt disease (i.e., a return to permanent normoglycemia) in 64-80% of mice. This remission was durable (> 4 months) and was not associated with the disappearance of insulitis (mononuclear cell infiltration of the islets). The immunosuppression was apparently specific for beta-cell-associated antigens, since mice showing anti-CD3-induced remission rejected histoincompatible skin grafts normally, whereas they did not destroy syngeneic islet grafts, unlike control untreated overtly diabetic NOD females. These results open major therapeutic perspectives. They strongly suggest that self-tolerance can be restored in adult mice once autoimmunity is fully established and confirm that this effect can be obtained by transient targeting of the CD3/T-cell receptor without massive T-cell debulking.

Animals↗

PubMed1979

Acute leukemia: biology and treatment.

A fundamental abnormality in acute myeloid leukemia is a block in cell differentiation with resultant accumulation of immature leukocytes. This abnormality can be studied in continuously growing leukemic cell lines that differentiate with simple chemical signals. Surface antigenic modulation occurring with cell differentiation can be monitored by specific antisera. These antisera have great potential as diagnostic and therapeutic reagents. More than 90% of patients with acute lymphoblastic leukemia and more than 70% of patients with acute myeloid leukemia can achieve remission of disease with aggressive multiagent chemotherapy. Long-term, disease-free survival is obtainable in about one half of patients with acute lymphoblastic leukemia but in less than 15% of patients with acute myeloid leukemia. The future directions of research for achieving cure of acute leukemia seem to be well defined.

Antigens, Neoplasm↗

PubMed1986

Structure/function studies of the common acute lymphoblastic leukemia antigen (CALLA/CD10) expressed on human neutrophils.

The common acute lymphoblastic leukemia antigen (CALLA/CD10) is a nonintegral membrane glycoprotein expressed on normal and neoplastic cells of hematopoietic and nonhematopoietic origin. We have undertaken a series of experiments to examine 1) the structural homology between leukemia cell and neutrophil CALLA/CD10 and 2) the putative function CALLA/CD10 subserves to human neutrophils. Biosynthetic labeling, peptide mapping, and two-dimensional gel electrophoresis indicate that neutrophils synthesize and express a CALLA/CD10 molecule that is similar, but not identical, to leukemic cell CALLA/CD10. The level of CALLA/CD10 expression is similar on the two cell populations, and neutrophil CALLA/CD10 (like its leukemic cell counterpart) undergoes antigenic modulation. Finally, we report that neutrophil cell surface-bound anti-CALLA/CD10 monoclonal antibodies inhibit the chemotactic response to both N-Formyl-methionyl-leucyl-phenylalanine (F-mlp) and zymosan-activated sera (ZAS), but had no inhibitory effect on random migration, degranulation, or aggregation. The anti-class I monoclonal antibody W6/32 exerted a similar effect on chemotaxis. We conclude that CALLA/CD10 has no clearly defined role in neutrophil function but may play a role in some distal event in chemotaxis.

Antibodies, Monoclonal↗

PubMed1989

Monoclonal antibodies which react with the T cell receptor gamma/delta recognize different subsets of CD3+WT31- T lymphocytes.

A polyclonal CD3+4-8-WT31- cell line (termed SFG) was utilized for mice immunization in order to produce monoclonal antibodies (mAb) specific for the T cell receptor (TcR) gamma/delta. Hybrid supernatants were screened for their ability to induce SFG cells (but not conventional TcR alpha/beta + CTL lines) to kill the murine Fc receptor-positive P815 target cell line. Three hybrids, termed G1, A13 and F11, were isolated according to this screening. By indirect immunofluorescence G1 mAb reacted with 65% of SFG cells, while A13 stained 26% and F11 75% of cells. Double-fluorescence analysis revealed that G1 and A13 mAb identify two distinct, non-overlapping subsets of cells present in the SFG cell line. The reactivity of the mAb was also analyzed on a panel of representative TcR gamma/delta clones. G1 mAb reacted with 5 clones, that were also stained by the previously described BB3 mAb (recognizing the disulfide-linked form of TcR gamma/delta). These clones failed to react with A13 and delta-TCS-1 mAb (the latter of which is known to react with a non-disulfide-linked form of TcR gamma/delta). Out of six clones that reacted with A13 mAb, four were also delta-TCS-1+, whereas two were delta-TCS-1- and none of them reacted with G1, (or BB3) mAb. In contrast to the mAb above, F11 brightly stained the G1+A13- clones and more weakly the G1-A13+ clones. Moreover, F11 efficiently triggered both types of clones to kill the P815 target cells while G1 and A13 were able to trigger only G1+ or A13+ clones, respectively. None of the mAb above reacted with a large number of CD3+WT31+ clones. Antibody-induced surface antigen modulation experiments indicated that molecules recognized by G1, A13 and F11 were physically associated on cell surface with CD3 determinants. In addition, immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis (performed on 125I-surface-labeled TcR gamma/delta+ clones) revealed that molecules recognized by G1, A13 and F11 displayed an apparent mol. wt. corresponding to that of CD3-associated TcR molecules, immunoprecipitated by anti-CD3 mAb from the same clones.

Animals↗

PubMed1988

Use of syngeneic monoclonal antibodies in the therapy of disseminated myeloid leukemic cells.

A syngeneic monoclonal antibody (MAb) (IC5F5) was successfully used in the immunotherapy of Rauscher-virus-induced myeloid leukemic RMB-I cells. It is directed to a virus-encoded, but aberrantly processed protein, which is expressed on the cell membrane. When applied in vivo, it binds only to RMB-I tumor cells. BALB/c mice were inoculated i.p. or i.v. with 10(7) RMB-I cells and died within 2-3 weeks due to increasing tumor load. Mice inoculated i.p. were completely cured by daily injections of ascites containing IC5F5. Disseminated tumor cells in liver and hemopoietic organs were observed after i.v. inoculation. Daily treatment with MAbs resulted in survival beyond 90 days. No antigenic modulation was observed when tumor tissue was analyzed 2-10 days after treatment. Treatment was successful even when therapy was postponed until day 5 following inoculation of tumor cells. When the number of ascites injections was reduced, survival was identical to that observed among repeatedly treated mice. Ten- and 100-fold dilution of ascites fluid diminished the number of survivors, but still resulted in a median survival time of 38 and 20 days, respectively, as compared to 14 days for untreated mice.

Animals↗

PubMed1985

Anti-lymphocyte antibodies in systemic lupus erythematosus.

Patients with systemic lupus erythematosus frequently develop antilymphocyte antibodies as measured by complement-dependent cytotoxicity and immunofluorescence assays. Highest titres of both of the major IgM and IgG classes occur during phases of active disease, and their presence is associated with essentially the entire spectrum of immune system functional abnormalities in this disorder. While the full range of antibody specificities requires further clarification, antibodies to many discrete lymphocyte populations have been described, including B cells, T cells, and T cell subsets. Antibodies to T cell subsets are of special interest because of their relationship with subset depletion in vivo, and their capacity to reproduce, through effects on normal cells in vitro, the same types of immunoregulatory abnormalities characteristic of lymphocytes isolated from patients with SLE. Suppressor/inducer and suppressor/effector T cells appear to be the main targets in this regard. Antibodies specific for activated T lymphocytes exist as well, and this type has the unusual property of interfering with events operant in production of/response to interleukin-2, a critical step controlling the expansion of specifically-reactive T cells and the induction of other lymphokines. In addition to complement-mediated lysis and antibody-dependent cell-mediated cytotoxicity, anti-lymphocyte antibodies have the potential to influence immune system function by several non-cytotoxic mechanisms, including surface antigen modulation and ligand/receptor triggering. Despite the large amount of data which has been accumulated concerning the cell type specificity and functional effects of anti-lymphocyte antibodies in SLE, little is known about the nature of the surface membrane molecules with which they react. Application of cell cloning and molecular biology technology should rectify this deficiency in the near future. Although it is likely that antilymphocyte antibodies are of relevance to immune system pathophysiology in SLE, it remains to be determined whether these interesting antibodies reflect secondary events, or have some more fundamental significance.

Antibody Specificity↗

PubMed1990

[Comparative study of TRBC receptor and E receptor on T lymphocytes of human and macaque].

In 1985, rosette formation of human and macaque pan-T lymphocytes with tree shrew red blood cells (TRBC) (TRBC rosette) was first found by Ben K et al, showing different physico-chemical properties from that of rosette formation with sheep red blood cells (E-rosette). In order to approach the correlation between TRBC receptor, E receptor (CD2) and other differentiation antigens (CDs) on T lymphocytes, rosette inhibition assay and antigenic modulation or co-modulation were performed with monoclonal antibodies (McAbs) to CDs, and the distribution of TRBC receptor in other peripheral immunocytes, cell lines was also examined. TRBC rosette appeared in 88.8% of E rosette positive peripheral blood lymphocytes (E(+)-PBL) and in 4.16% of E(-)-PBL. TRBC receptor was also found on all T cell lines tested (CEM, H33 HJ-JA 1, Jurkat, MLA-144, Molt-3, Molt-4, Molt-4 clone 8, PEER) and some myeloid lines (U 937 and HL 60), but not on human granulocytes, B cell lines (Daudi, Raji and Reh) and myeloid line K 562. The modulation or co-modulation of CD 3, TCR, CD 5, CD 6 and CD 7 with McAbs OKT 3, T 108 (F 1), T 136 (F 101-15), T 149 (M-T 604) and T 152 (7 G 5) did not affect TRBC rosette formation of PBL. TRBC rosette of human and rhesus monkey PBL was not inhibited by T 11.1 McAb OKT 11 (CD 2 McAb), in contrast human and rhesus monkey E rosette formations were obviously blocked at inhibition rates of 77.9% and 49.3%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Endopeptidase inhibition and intestinal antigen processing in mice.

The role of gastrointestinal digestive processes in the systemic availability of ingested protein antigens was examined by feeding the trypsin inhibitor aprotinin intragastrically to mice and measuring uptake of ovalbumin and 14C-polyethylene glycol (MW 4000) from the gastrointestinal tract. Trypsin and chymotrypsin activities in the intestinal lumen were significantly reduced by aprotinin feeding. Aprotinin slowed stomach emptying, but radioimmunoassays for immunoreactive ovalbumin in the serum of mice prefed aprotinin showed 12-fold elevations within 1 hr after ovalbumin feeding. Uptake of a nonmetabolized macromolecular probe, 14C-polyethylene glycol-4000, increased less than two-fold when fed with aprotinin under the same conditions, indicating that the increased uptake of immunoreactive ovalbumin was not due to changes in intestinal permeability. The results show that inhibition of luminal proteolysis caused significant increases in the serum concentration of immunoreactive ovalbumin, indicating that acute inhibition of luminal proteases permits larger quantities of relatively intact protein to interact with mucosal absorptive surfaces. These results support the hypothesis that pancreatic proteases modulate antigen absorption from the lumen in adult animals.

Animals↗

PubMedDate not supplied

Bispecific Ab therapy of B-cell lymphoma: target cell specificity of antibody derivatives appears critical in determining therapeutic outcome.

Despite the success of mAb and bispecific (bs)Ab in the treatment of certain malignancies, there is still considerable uncertainty about the most appropriate format in which they should be used. In the current work we have investigated a panel of bsAb [IgG and F(ab)2] with dual specificity for T cells and neoplastic B cells. Throughout this work, anti-CD2 or anti-CD3 were used to bind the mouse T cells, and antibodies to surface IgM idiotype (Id), CD19, CD22, or MHC class II were used to target mouse B cell lymphomas BCL1 or A31. In vitro, killing was measured in a conventional cytotoxicity assay using 51Cr-labelled A31 and BCL1 cells as targets and activated mouse splenocytes as effectors. bsAb showed a wide range of cytotoxic activities, which could be ranked in the following order: [anti-CD3 x anti-class-II] > [anti-CD3 x anti-CD19] > [anti-CD3 x anti-Id] > [anti-CD3 x anti-CD22], with the [anti-CD2 x anti-Id] derivative showing relatively little cytotoxic activity. This hierarchy of activity indicates some correlation with the binding activity of the bsAb on target cells, but showed a much stronger parallel with the tendency of the anti-(target cells) mAb to undergo antigenic modulation (less modulation, more killing). In vivo, the situation was completely different and only the anti-Id derivatives, [anti-CD3 x anti-Id] and [anti-CD2 x anti-Id], were effective in prolonging the survival of tumour-bearing animals. Under optimal conditions Id-positive tumour was eradicated with a single treatment of bsAb. We conclude from this work that the target cell specificity of a bsAb is critical in determining therapeutic outcome and that in vitro cytotoxicity assays do not predict in vivo activity.

Animals↗

PubMed1995

An analysis of the role of skin Langerhans cells (LC) in the cytoplasmic processing of HIV-1 peptides after "peplotion" transepidermal transfer and HLA class I presentation to CD8+ CTLs--an approach to immunization of humans.

Skin Langerhans cells (LC) are antigen-presenting cells capable of expressing MHC class I and class II molecules on the plasma membrane. This molecular activity was reviewed to combine the knowledge of peptide presentation by MHC and HLA class I and class II molecules to prime CD8+ cytotoxic T cells (CTLs) and CD4+ T helper cells, respectively. The possible utilization of the skin dendritic cells for the development of antiviral CTLs and antibodies by synthetic peptides modeled according to the motifs of peptides that naturally interact with the peptide binding grooves of the various HLA haplotypes is discussed and evaluated. It may be possible that the introduction of synthetic viral peptides with motifs to fit the HLA class I haplotypes of a human population to the skin dendritic cells will prime selectively the cellular or the humoral immune responses. This approach may provide a new vaccination technique that applies synthetic virus peptides as vaccines for the immunization of humans. The neuropeptide CGRP interacts with LC and modulates antigen presentation.

Antigen Presentation↗

PubMed1983

Migration of B and T lymphocytes to M cells in Peyer's patch follicle epithelium: an autoradiographic and immunocytochemical study in mice.

Intimate interaction occurs between M cells which take up antigens in Peyer's patch epithelium and underlying lymphocytes but the migratory pathway and subtypes of these lymphocytes have remained uncertain. Lymphocyte homing to Peyer's patches was investigated by separating mouse splenic B and T lymphocytes, labeling with [3H]adenosine, reinjecting into syngeneic mice, and localizing them by autoradiography after 17, 40, and 68 hr. Both B and T lymphocytes migrated across postcapillary venules through intercellular spaces. Most labeled cells of both types localized around postcapillary venules in the initial time period, then migrated through the lymphoid mass to follicle epithelium. T-cell number in follicle epithelium peaked at 17 hr but B cells peaked at 40 hr. At each time point more labeled B than T lymphocytes were found below M cells and in follicle epithelium but the differences were only significant (P less than 0.01) at 40 hr. Endogenous B lymphocytes, identified by antibody staining, were also associated with M cells, possibly reflecting a role for secretory antibody in modulating antigen uptake.

Animals↗

PubMed1982

Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma.

The generation of murine monoclonal antibodies reactive with human leukemia and lymphoma cells has recently led to clinical trials that have begun to evaluate the use of these reagents in the treatment of various leukemias and lymphomas. Several of these studies have demonstrated that infusion of monoclonal antibody can cause the rapid and specific clearance of leukemic cells from the peripheral blood. Intravenously administered antibody also rapidly binds to bone marrow lymphoblasts, and in one instance, has resulted in the partial regression of tumor cell infiltrates in lymph nodes and skin. Unfortunately, clinically significant responses have not in general been achieved, but these clinical studies have identified specific factors that result in the development of resistance to antibody-mediated lysis in vivo. These factors include the presence of circulating antigen, antigenic modulation, reactivity of monoclonal antibody with normal cells, immune response to murine antibody, and the inefficiency of natural immune effector mechanisms. Current research is now being directed towards developing methods to circumvent each of these obstacles. Future clinical studies utilizing antibodies in vitro or with different specificity may demonstrate greater therapeutic efficacy. In addition, monoclonal antibodies can be used as carriers of other cytotoxic agents and in conjunction with other agents that will reduce the total load. Monoclonal antibodies represent new and powerful reagents that may in the near future become an additional therapeutic modality for patients with malignant disease.

Animals↗

PubMed1987

Molecular nature of a cell membrane antigen specific for human T-cell acute lymphoblastic leukemia.

In the present work, we characterized the molecular nature of a T-cell acute lymphoblastic leukemia (T ALL) specific antigen, termed TALLA, which is defined by monoclonal antibody SN1. SN1 shows an extremely high specificity for T ALL. In the present study, SN1 was further shown not to react significantly with various normal solid tissues. TALLA was determined to be a glycoprotein with an approximate molecular weight of 150,000. However, the molecular nature of TALLA is peculiar in that heating at 100 degrees C for 2 min renders TALLA undetectable in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It should be noted that such heating is a common practice before analysis of proteins and glycoproteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No significant antigenic modulation of TALLA was observed when T ALL cells were reacted with SN1. Two new monoclonal antibodies, SN1a and SN1b, which show the same cell binding specificity as SN1 were also generated in the present work and compared to SN1. Competitive binding experiments showed that the epitopes on TALLA recognized by SN1, SN1a, and SN1b are sufficiently close to one another to allow complete reciprocal inhibition of antibody binding. These epitopes apparently became more exposed to antibody when T ALL cells were treated with neuraminidase; neuraminidase-treated T ALL cells bind 29-35% more SN1, SN1a, and SN1b as compared to the original T ALL cells.

Antibodies, Monoclonal↗

PubMed1981

Factors affecting the susceptibility of different strains of mice to experimental myasthenia gravis.

Mice immunized with purified AChR (T. californica) invariably form anti-AChR antibodies and often develop a condition of extreme muscular weakness and flaccid paralysis. Pharmacological, physiological, and ultrastructural studies indicate that the pathophysiology of EMG in the mouse closely resembles that of human MG. The single episode of muscular weakness typically found in mouse EMG differs from the acute phase of rat EMG in that macrophages and other phagocytes do not appear to play an active role in the destruction of the neuromuscular junction. The frequency of paralysis in mice immunized with AChR is highly strain dependent and is not attributable to polymorphisms with respect to susceptibility to cholinergic blockade. The incidence of paralysis does not correlate with the magnitude of the humoral response to either T. californica or mouse AChR. Because both paralyzed and nonparalyzed mice form antibodies which are able to increase the rate of both junctional and extrajunctional AChR degradation, the mere presence of antibodies reactive with cell surface antigenic determinants of AChR is not sufficient for the induction of paralysis. While it is still possible that antibody-induced degradation of AChR may be necessary for the induction of paralysis, these studies rule out the possibility that antigenic modulation of AChR is sufficient to account for the induction of paralysis in mouse EMG. In the present studies alleles of the two loci were identified which significantly effect the probability with which mice immunized with AChR can be expected to become paralyzed, the MHC and the IgCH region. Because one genotype, H-2b, Ig-1b segregated with high susceptibility to EMG in four strains derived from three dissimilar backgrounds, these studies strongly suggest that susceptibility to the development of paralysis is a heritable trait determined by regions of the mouse genome which regulate immune responsiveness.

Animals↗