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PubMed2001

Binding properties of the mannose receptor.

A comprehensive approach to the study of mannose receptor (MR) biology has unveiled an unexpected level of complexity and stresses the importance of post-translational modifications and gene regulation in the analysis of protein function. The existence of endogenous tissue ligands for the MR highlights the need to reduce MR expression in antigen presenting cells and/or to regulate T cell stimulation after presentation of MR ligands, in order to avoid autoimmunity. This regulation might be achieved by down modulation of the antigen presenting cell stimulatory capacity upon MR ligation. In macrophages there are conflicting evidence regarding the outcome of MR recognition. These results are not unexpected if endogenous mannosylated and sulphated self-antigens, that need to be shielded from the immune system, are being eliminated through this receptor. The presence of counter receptors for the cysteine rich (CR) domain of the MR in specialized myeloid cells in lymphoid organs adds a new dimension to this system. It opens the possibility for a delivery pathway for MR carbohydrate recognition domains (CRDs) ligands that needs to be investigated further.

Animals↗

PubMed1986

Modulation of IgM anti-lymphocyte antibody-reactive T cell surface antigens in systemic lupus erythematosus.

Cold-reactive lymphocytotoxic autoantibodies are present in the serum of most patients with active systemic lupus erythematosus (SLE) and may be important for the development of the lymphopenia and T cell dysfunction characteristic of this disorder. Neither the mechanisms of autoantibody action in this regard, nor the nature of the relevant T cell membrane target molecules have been defined, however. In the present investigation, preincubation of T cells with SLE serum at 37 degrees C reduced their reactivity with SLE IgM anti-lymphocyte autoantibodies, as demonstrated by indirect immunofluorescence and complement-dependent cytotoxicity. Modulation was restricted to SLE IgM autoantibody-reactive antigen; monoclonal antibody staining of various T cell differentiation and activation antigens remained unchanged. Loss of antigen from the surface membrane was rapid, but transient. A nadir was reached after approximately 120 min of 37 degrees C incubation, followed by essentially complete reexpression of antigen several hours later. Although modulation occurred spontaneously at 37 degrees C in the absence of SLE serum, loss of antigen was enhanced by IgM anti-lymphocyte autoantibodies, despite their low thermal amplitude. Modulation was inhibited by sodium azide, by fixation of cells with paraformaldehyde, and by low incubation temperatures. Colchicine and cytochalasin D had no effect on this process, suggesting that the integrity of the cytoskeleton was not essential. Cycloheximide did not prevent loss of antigen, but inhibited its reexpression. In experiments to determine the fate of modulated antigen, both intracytoplasmic accumulation and shedding from the cell surface were demonstrated. Only shedding was increased by the presence of anti-lymphocyte antibodies, however. These studies delineate modulation of T cell membrane antigen as a new mechanism for anti-lymphocyte autoantibody action in SLE. The occurrence of modulation at physiologic temperatures in vitro suggests that a similar phenomenon of potential relevance to T cell dysfunction may obtain in patients with this disorder.

Antigen-Antibody Reactions↗

PubMed1995

Multidrug transporter P-glycoprotein 170 as a differentiation antigen on normal human lymphocytes and thymocytes: modulation with differentiation stage and during aging.

P-glycoprotein 170 (P-gp), the multidrug transport pump, excludes drugs from the interior of cells and is inhibited by agents such as cyclosporin A (CsA), verapamil, and FK-506, which are also substrates for the P-gp pump. This work documents the age- and differentiation-related changes in P-gp on T and B lymphocytes from human blood or spleen, and its absence on most thymus and bone marrow cells. Analysis of rhodamine 123 (Rh123) dye efflux, and its inhibition by cyclosporin A, was used as a quantitative measure of functional P-gp, and reactivity with MRK-16 was used as a measure of P-gp surface expression. The dye efflux and phenotypic expression of P-gp+ PBMC appeared equivalent to that of a moderately drug-resistant cell line, although efflux is prolonged. The sensitivity to inhibition by CsA, cyclosporin G (CsG), and PSC833 of P-gp on PBMC, thymocytes, or T-cell lines varied with apparent cell-type specificity. Normal blood and splenic T- or B-cells included 50-80% of cells with surface P-gp (MRK-16+), which mediated CsA-sensitive dye export. The proportion of P-gp+ T- and B-cells was lowest among children under age 10 years, increased in adulthood, and decreased after age 60. Thymus included 30% of P-gp+ cells mediating CsA-sensitive dye export, including CD3-4-8- progenitors and mature CD3hi CD4+8- or CD4-8+ thymocytes. Mature T-cells in cord or adult blood, spleen, and bone marrow included a large proportion (50-60%) with efficient CsA-sensitive dye export, preferentially among the CD45RA+ subset. Monocytes from all tissue sources, and most bone marrow cells, expressed surface P-gp but retained Rh123, suggesting the absence of a functional dye export mechanism. In vitro mitogen-stimulated PBMC T and B lymphocytes lost P-gp function within 4-24 hr, consistent with the observation that P-gp was reduced on antigen-experienced CD45R0+ T-cells in vivo. Drug export by P-gp may protect lymphocytes from toxic effects of CsA, and may contribute to the immunosuppressive effects of such drugs. The developmentally regulated expression of P-gp function on lymphocytes, and its modulation on activated T- or B-cells, suggest an important role in normal immune development.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1981

Carcinoma-associated cytostructural antigenic alterations: detection by lectin binding.

Tumor cell membrane glycoproteins may be involved in the induction of tumor immunity or in the escape of tumors from immunologic defense mechanisms. Previous investigations have suggested a role for blood group antigens and their precursors, in the generation of the immune response to neoplasia. In this study, 44 benign and malignant breast lesions were examined for the presence of a carbohydrate precursor antigen (T-antigen) of the human blood group system MN. T-antigen was demonstrated using an immunohistochemical technique to detect tissue binding of a plant lectin (PNA) with specificity for T-antigen. Of the 22 benign breast lesions examined, 19 showed T-antigen present along the luminal cytoplasmic membrane and occasionally on intraluminal secretions. T-antigen, as demonstrated by lectin binding, was confined to this region in all benign lesions except one, which also showed cytoplasmic positivity. Malignant breast lesions showed a pattern of T-antigen expression markedly different from that of benign breast tissues. Of 22 breast carcinomas, 17 showed diffuse cytoplasmic T-antigen. Five carcinomas showed no evidence of T-antigen by this technique. These malignancies tended to be the most poorly differentiated when judged by histologic criteria. A possible role for T-antigen in the modulation of the immune response to breast carcinoma is suggested.

Antigens, Neoplasm↗

PubMedDate not supplied

Stimulation of tumor cell growth in vitro by a monoclonal antibody to a tumor specific protein (TSP-180) present on the cell surface of 3LL cells.

Proliferation capacity and MHC class I antigen expression of two Lewis lung carcinoma (3LL) metastatic variants (C87, BC215) grown under defined experimental conditions (serum-free defined medium or 10 per cent serum) have been studied following exposure to MoAb 135-13C which recognizes on these cells a tumor surface protein of 180,000 daltons (TSP-180). The results of this study indicate that the high metastatic clone (C87) binds higher amounts of MoAb to TSP-180 and Db antigens than does the low metastatic one (BC215), while both clones express very low amounts of Kb antigens. 3LL clones grown in 10 per cent serum or adapted in serum-free, defined medium show the same metastatic phenotype and MHC class I antigen expression, but when grown in defined medium exhibit increased capacity to bind MoAb 135-13C. However, the relative binding rate of 3LL clones grown in 10 per cent serum or in defined medium is unchanged: the high metastatic clone always showing higher capacity to bind MoAb to TSP-180. Furthermore, comparison of EGF binding sites on the cell surface of 3LL clones, grown in different culture conditions, demonstrates that the C87 clone binds higher amounts of labelled EGF and that this amount increases in serum-free defined medium, exactly as reported for TSP-180. In addition, competition experiments demonstrated that MoAb 135-13C does not compete for EGF binding sites on 3LL cell surface. Studies on cell proliferation following exposure to MoAb 135-13C, revealed that the low metastatic clone (BC215) is more actively stimulated than the high metastatic one. Moreover, similar data were obtained after exposure of 3LL clones to physiological amounts of different growth factors (i.e. EGF, MSA, insulin). Analysis of MHC class I antigen expression following exposure to MoAb 135-13C indicated that MoAb 135-13C induces on the cell surface of the C87 clone a transient low modulation of Db antigens. These results suggest that 3LL cells endowed with lower metastatic potential are more dependent on the microenvironmental conditions than the high metastasizing ones, and that MoAb 135-13C binding to 3LL cell surface stimulates proliferation as reported for several known growth factors.

Animals↗

PubMed1980

Cytostructural localization of a tumor-associated antigen.

Tumor cell membrane glycoproteins may be involved in the induction of tumor immunity or in the escape of tumors from immunologic defense mechanisms. Forty-four benign and malignant breast lesions were examined for the presence of a carbohydrate precursor antigen (T antigen) of the human blood group system MN. T antigen was demonstrated by means of an immunohistochemical technique to detect tissue binding of peanut agglutinin, a plant lectin, with affinity for T antigen. Malignant breast lesions showed a pattern of T antigen expression different from that of benign breast tissues. A possible role for T antigen in the modulation of the immune response to breast carcinoma is suggested.

Antibody Formation↗

PubMed1987

Differential induction of lupus associated antinuclear antibodies in MRL mice by monoclonal anti-Sm antibodies.

The effect of monoclonal autoantibodies on immunoregulation was investigated in MRL/MpJ-lpr/lpr mice. Passive transfer of KSm2 (a monoclonal IgG2a antibody directed against the 16 kD polypeptide of Sm) induced IgG antibodies to the other major immunoreactive polypeptides of Sm (28 and 29 kD) in all mice studied, and to polypeptides of the closely related antigen nRNP/Sm in 63% of the mice. In addition an increment in IgG anti-dsDNA antibodies, and in IgA and IgM anti-Sm antibodies, over control levels was observed. These effects were not due to polyclonal activation since anti-histone antibody levels were unaffected. Two other IgG2a monoclonal antibodies: KSm5 (directed against the 28 and 29 kD Sm polypeptides) and OX 12 (directed against an irrelevant antigen) failed to modulate the autoimmune responses of the mice in any way. These results demonstrate specific antibody-mediated connectivity between B cell clones producing autoantibodies against three distinct antigens.

Animals↗

PubMed1994

Modulation of signaling via the B cell antigen receptor by CD21, the receptor for C3dg and EBV.

CD21 is the receptor for C3dg and EBV. Several reports have shown that these CD21 ligands, and certain anti-CD21 mAb, trigger B cell activation, particularly when combined with Ag receptor ligation. However, the characteristics, biologic functions, and importance of this CD21-signaling pathway are unknown. We have used a model we recently developed to study B cell activation induced by complex particulate Ag, such as immune complexes and viruses, to begin to examine these questions. In the current studies, we incubated purified small resting B cells with 100-nm latex beads bearing various combinations of CD21 ligands and mAbs to CD19, CD35, and the Ag receptor. CD21, CD19, and CD35 have all been implicated in modulating membrane IgM initiated signaling. Beads coated with mAb to the C3dg/EBV-binding portion of CD21, but not mAb to other portions of the CD21 molecule, triggered B cell homotypic aggregation. Beads coated with the same CD21 ligands, although inactive alone, synergized with anti-IgM mAb in greatly increasing (20- to 180-fold) mRNA levels of the c-fos nuclear proto-oncogene. Signaling via CD21 was tyrosine kinase dependent. Levels of c-myc mRNA were not altered by CD21 ligands. Anti-CD19 and anti-CD35 mAb did not augment signaling via membrane IgM as assessed by changes in c-fos mRNA levels. These findings indicate that CD21 ligands binding to the C3dg/EBV-binding site of CD21 markedly augment B cell activation initiated by Ag receptor ligation via a selective, c-fos-dependent signaling pathway.

Antibodies, Monoclonal↗

PubMed1990

Evaluation of Ia expression in rat ocular tissues following inoculation with interferon-gamma.

It is becoming increasingly clear that IFN-gamma is a potent immunoregulatory protein which influences MHC class II (Ia) antigen expression and cellular functions of B cells, T cells, NK cells and macrophages. During the past 5 yr our laboratory has provided evidence that IFN-gamma modulates class II antigens on retinal cells (retinal pigment epithelial cells, endothelial cells) and is localized within the eye during human inflammatory conditions. In this study we evaluate the direct effect of IFN-gamma on ocular tissue. Lewis rats were inoculated intravitreally or under the retina with either recombinant IFN-gamma (20,000 U) or saline. At 2 hr, 1, 2 and 6 days postinoculation, the eyes were removed and frozen sections were evaluated by immunocytochemical staining with monoclonal anti-Ia antibodies and an irrelevant monoclonal anti-T cell antibody. Saline treated tissue and tissue removed 2 hr after IFN-gamma inoculation showed no significant staining for Ia antigens. However, eyes evaluated 24 hr after IFN-gamma inoculation revealed Ia expression on a variety of ocular cells localized in the conjunctiva and anterior segment, such as conjunctival epithelium, keratocytes, iris epithelium, ciliary epithelium and choroidal cells. In the retina, retinal pigment epithelial (RPE) cells were Ia positive only when IFN-gamma was injected directly under the retina. In conjunction with Ia expression, two striking changes were noted. An iritis was seen and infiltrating cells were detected in the inner retinal layers. Both of these phenomena have been observed in certain inflammatory eye diseases. These studies clearly substantiate the concept that IFN-gamma can regulate class II antigens in the eye and thus may perpetuate immune reactivity in this site.

Animals↗

PubMed1990

Lymphocyte mitogenesis and CD4 modulation induced by different phorbol esters: comparative studies.

Phorbol 12-myristate 13-acetate (PMA) can stimulate T-cells via its binding to protein kinase C (PKC). Such a phenomenon occurs when a threshold of concentration as low as 1 nM of PMA is reached. Other phorbol esters possess the ability to stimulate lymphocytes but at higher thresholds of concentration. We show here that the different phorbol ester concentrations needed to induce stimulation and proliferation, estimated by both interleukin-2 receptor (IL-2R) expression and DNA synthesis, correspond very closely to those inducing the modulation of CD4 antigen, confirming a direct relationship between CD4 down-regulation and cellular activation. We estimated the structural features of these different phorbol derivatives in relation to lymphocyte activation and CD4 modulation, and confirm that the ester side chains which give to the phorbol ester derivatives their lipophilic character, discriminate, according to their length, the ability of the different compounds to reach their receptor inside the cell membrane; we also brought some evidence that the polar phorbol nucleus of these compounds is probably responsible for their interaction with the membrane receptor mainly through the hydroxyl group in the C4 position.

Adult↗

PubMed1988

The relationship of modulation of major histocompatibility complex class I antigens to retrovirus transformation in rat cell lines.

The expression of major histocompatibility complex (MHC) Class I antigens has been studied, by means of monoclonal antibodies directed against nonpolymorphic determinants of MHC Class I molecules, in two epithelial differentiated cell lines (FRTL-5 clone 2 and PC clone 3) and in one fibroblast cell line (FRT Fibro) of Fischer rat thyroid origin, before and after infection with various acute retroviruses carrying the v-ras-Ha, v-mos, v-src, polyoma middle T, and c-myc oncogenes. The results obtained indicate that a single virus does not produce identical changes in MHC Class I molecule expression in all tested lines, but a general increase occurs in lines derived from FRTL-5 clone 2 and a decrease occurs in lines derived from PC clone 3 and from FRT Fibro. Thus the modulation of expression seems to proceed always in the same direction in each cell line regardless of the infecting retrovirus and appears to involve posttranscriptional mechanisms, since no modification of expression of mRNA levels has been observed between normal and transformed cells. Only one line of PC clone 3 origin, transformed by the cooperation of two oncogenes (human c-myc and middle T), almost completely lost MHC Class I antigens on the cell surface and presented a significantly reduced synthesis of Class I mRNA.

Animals↗

PubMed2002

Cross-reactivity and T-cell receptor antagonism of myelin basic protein-reactive T cells is modulated by the activation state of the antigen presenting cell.

The peripheral T-cell population is educated to recognize a maximum of pathogen-derived epitopes while ignoring self-antigens. As the total number of T-cell clones is limited, each T-cell receptor (TCR) needs to be cross-reactive in order to achieve a wide repertoire. This opens the possibility for T cells to diverge from their defending role and induce auto-aggression by mistake. The factors involved in the initiation of such autoimmune responses remain to be fully understood. In an attempt to assess the role of antigen presenting cells (APC) in the triggering of autoimmunity, we studied the cross-reactivity of TCR transgenic Tg4 T cells, reactive to the Ac1-9 peptide of myelin basic protein (MBP). Using different APC populations and a range of peptide analogues of Ac1-9, we found that the activation of APC enhanced the cross-reactivity of Tg4 cells, and that this effect could be mimicked by resting APC supplemented with exogenous co-stimulation. Further, we observed that the inhibitory effect of an antagonist peptide of the Tg4 TCR was greatly reduced when activated APC were used. However, when co-stimulation was blocked, TCR antagonism was restored to its normal level. Our results show for the first time that the activation of naturally occurring APC, namely dendritic cells, B cells and macrophages, can modulate the reactivity of T cells, both in terms of cross-reactivity and TCR antagonism, and that this effect is most likely due to enhanced levels of co-stimulation.

Animals↗

PubMed1986

Cholinergic modulation of an acetylcholine receptor-like antigen on the surface of chick ciliary ganglion neurons in cell culture.

Chick ciliary ganglion neurons have a membrane component that shares an antigenic determinant with the "main immunogenic region" of the alpha subunits in nicotinic ACh receptors from skeletal muscle and electric organ. Ultrastructural studies on antibody binding in the ganglion have shown that the cross-reacting antigen on the neuron surface is located predominantly in synaptic membrane. Biochemical studies have shown that the cross-reacting component has a number of other properties expected for the ganglionic nicotonic ACh receptor and that it is distinct from the alpha-bungarotoxin binding component in the tissue. Here we show that ciliary ganglion neurons grown in dissociated cell culture express a similar component that cross-reacts with monoclonal antibodies to ACh receptors, and that the number of antibody-binding sites on the neurons can be modulated by exposure to cholinergic agonists and a protein neurotoxin that reversibly inhibits ACh receptors on the neurons. In most, though not all, cases, levels of ACh sensitivity associated with the neurons are specifically comodulated in parallel with the changes in number of antibody binding sites. The results suggest that at least a portion of the cross-reacting sites on the surface of ciliary ganglion neurons is likely to represent nicotinic ACh receptors. The fact that in some instances levels of ACh sensitivity can be altered without changing the number of cross-reacting sites, however, leaves open the possibility that not all of the sites are associated with receptors or that the neurons can alter the proportion of receptors that is functional.

Animals↗

PubMed1990

Lymphokines and cytokines as cancer treatment. Immunotherapy realized.

Human proteins with identified effects on host responses to malignant cells have been established as effective therapeutic techniques in cancer. Lymphokines, products of activated cells of the immune system, have pleiotropic biochemical and cellular effects. These include stimulation of immune effector cell proliferation, augmentation of cytotoxicity of immune effector cells for tumor cell targets, enhancement in antigen-recognition potential by monocytes, and modulation of tumor-associated antigen expression on neoplastic cells. Interferons (IFN) and interleukin-2 (IL-2), purified to homogeneity, can induce regression of metastatic malignancy. Recombinant DNA technology has facilitated large-scale production of these and other lymphokines and cytokines. It has also made possible analyses of physical structures of the molecules themselves and has enabled creation of mutated molecules with specific, desired substitutions in their amino acid sequence. Monoclonal antibodies, directed at tumor-associated antigens, can augment antibody-dependent cell-mediated cytotoxicity and can selectively deliver cytotoxic techniques to malignant cells. Molecules that modify the host resistance to malignant disease also have potential to augment effectiveness of other cancer treatment techniques. Lymphokines, cytokines, and monoclonal antibodies, all products of biotechnology, have resulted in fulfillment of the promise of the immune system for inhibition of growth of human malignancy.

Animals↗

PubMed1991

Prolonged survival of skin grafts following treatment with an antibody to a putative cell triggering molecule, QCA-1.

The QCA-1 molecule (quiescent cell antigen-1) appears to be involved in the differentiation events undergone by T cell following occupancy of the antigen receptor. Here we show that modulation of the QCA-1 antigen from the surface of the cell normally follows activation, and that treatment of animals with the antibodies against the QCA-1 molecule inhibits the normal response to an allograft without appearing to alter the number of peripheral T cells or the expression by these cells of the alpha/beta T cell antigen receptor.

Animals↗

PubMed2001

Analysis of recombinant mycobacteria as T helper type 1 vaccines in an allergy challenge model.

The potential for development of mycobacteria as T helper type 1 (Th1) vaccines capable of induction of Th1 responses to recombinant antigens was explored in a model system based on an immunodominant peptide from house dust mite. Different recombinant mycobacterial preparations were compared for their ability to induce a Th1 response to the peptidea. It was found that mycobacterial viability was not a prerequisite for Th1 immunogenicity. A dominant interferon-gamma (IFN-gamma) response to peptide was observed in splenocytes from C57BL/6J mice immunized with live or heat-killed preparations of recombinant Mycobacterium vaccae or with live attenuated bacillus Calmette-Guèrin (BCG) vaccine expressing the antigen. Interleukin-5 (IL-5), a marker of a Th2 response, was detected only in mice receiving live M. vaccae. A similar pattern was observed in BALB/b mice, although the magnitude of the IFN-gamma response was much lower. Control and immunized mice were subsequently exposed to allergen using a Th2-inducing challenge protocol. A significant shift from a Th2 to a Th1 response was observed in immunized mice, as judged by cytokine expression by splenocytes and by subclass of circulating antibody. The effect was seen in three inbred mouse strains differing in their innate bias towards Th1 or Th2 responses. It was dependent on the presence of specific antigen in the mycobacterial preparation and, under the immunization conditions tested, was more pronounced with dead M. vaccae than with live BCG as carrier vaccine. The results demonstrate the potency of killed mycobacteria as Th1 adjuvants and suggest a potential application for recombinant mycobacteria in antigen-specific immune modulation.

Adjuvants, Immunologic↗

PubMed1988

Characterization and expression of the human T cell receptor-T3 complex by monoclonal antibody F101.01.

A murine monoclonal antibody (MoAb) F101.01 reacting with the T cell receptor (TCR)-T3 complex is presented. Immunohistological studies showed that F101.01 specifically stains T-zone lymphocytes in lymph nodes, tonsils, and splenic tissue. Two-colour immunofluorescence and flow cytometry demonstrated co-expression of the antigen defined by F101.01 and the pan-T cell antigens defined by CD2, CD3, CD5, and CD7 antibodies. Cells stained with CD4 and CD8 antibodies were both included in the F101.01-positive population, whereas CD16-positive natural killer cells (NK), B cells (CD19 and CD20), and myeloid cells (CD13 and CD33) were excluded. The target antigen of F101.01 co-modulated with the CD3-defined antigen (T3) and the TCR recognized by the MoAb WT-31. CD3 antibody and WT-31 both blocked binding of F101.01. F101.01 precipitated the TCR-T3 complex from lysates of 125I-labelled peripheral blood mononuclear cells (PBMC) and HPB-ALL, when the lysate was prepared with a detergent (digitonin) that conserves the TCR-T3 complex. FACS analysis of T cells from a patient with a T cell immunodeficiency demonstrated that delta-TCS-1-CD3+CD4+ and delta-TCS-1-CD3+CD8+ cells were brightly F101.01+, whereas a large subpopulation of delta-TCS-1+CD3+CD4-CD8- cells were weakly F101.01+. We conclude that F101.01 recognizes a conformational epitope of the TCR-T3 complex and that it reacts with the alpha beta TCR-T3 and the gamma delta TCR-T3 complexes with different intensities.

Antibodies, Monoclonal↗

PubMed1987

Phosphorylation of polyomavirus large T antigen: effects of viral mutations and cell growth state.

Phosphorylation is responsible for the shift in electrophoretic mobility of polyomavirus large T antigen observed in pulse-chase or continuous-labeling experiments. Phosphorylated forms migrated more slowly than newly synthesized [35S]methionine large T antigen, and alkaline phosphatase treatment reversed the mobility shift. Analysis of phosphopeptides with Staphylococcus aureus V8 protease showed that large T antigen forms of intermediate mobility were enriched in peptides 1 to 4, 8, and 9, while the slower migrating species had all nine phosphopeptides, including peptides 5 and 7. The phosphorylations represented by phosphopeptides 5 and 7 were of particular interest. These phosphopeptides were entirely lacking in large T antigen from tsa mutants such as ts616 labeled at the nonpermissive temperature. Also, the phosphorylation of peptides 5 and 7 depends on the growth state of the cell. Early in infection of quiescent cells intermediate mobility forms of large T antigen with little or no phosphorylation, particularly of peptides 5 and 7, were seen, whereas peptides 5 and 7 were well represented at the same time in patterns from growing cells. Later in infection of growth-arrested cells, these phosphorylations were observed, suggesting that infection stimulates the relevant kinase. Because large T antigen of hrt mutants, which lack middle and small T antigens, showed phosphorylation of peptides 5 and 7, large T antigen was apparently responsible for the stimulation. Because some differences in the distribution of phosphopeptides were noted between hrt mutants and the wild type, middle T antigen, small T antigen, or both may play a modulating role in large T antigen phosphorylation.

Alkaline Phosphatase↗