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K Guy

Publications and source records attributed to K Guy.

48 records · Page 3Linked to original sources
PubMed1982

Differential expression and serologically distinct subpopulations of human Ia antigens detected with monoclonal antibodies to Ia alpha and beta chains.

Studies with two monoclonal antibodies (DA6.147 and DA6.231) which react, respectively, with isolated human Ia alpha and beta chains are reported. Both antibodies detect epitopes expressed on all DR-heterozygous and DR-homozygous cell lines tested (n = 17) and bind to the Epstein-Barr virus-negative cell line Ramos. Ia subunit specificity of the antibodies was determined by an adaptation of an electroblot technique which transfers separated Ia chains from polyacrylamide gels to nitrocellulose paper. In radioimmunobinding assays, peripheral blood B cell-enriched fractions, phytohemagglutinin-activated T cells and pokeweed mitogen-activated cells gave strong reactions with DA6.231 (anti-Ia beta). In contrast, DA6.147 (anti-Ia alpha) reacted only weakly, if at all, with peripheral B cells, pokeweed mitogen blasts and activated T cells. However, both antibodies bound to isolated Ia from activated T cells and peripheral B cells after Nonidet-P40 solubilization of the cells and DA6.147+ antigens could be found in the cytoplasm of activated T cells by indirect immunofluorescence techniques. Results of serological inhibition procedures following fractionation of lymphoblastoid cell lysates on monoclonal antibody affinity columns showed that the DA6.147 alpha chain epitope is carried on only a minor subpopulation of human Ia.

Antibodies, Monoclonal↗
PubMed1982

Human MHC class II molecules as differentiation markers.

DA6.231 and DA6.164 are mouse monoclonal antibodies that immunoprecipitate HLA-DR-like p34,29 glycoprotein dimers from surface- and metabolically-labeled cells. On lymphoblastoid cell lines the distribution of the 231 epitope is completely nonpolymorphic, while the 164 epitope is present on all cells except on those that are DR7 homozygous. Binding-inhibition studies show that the 231 and 164 epitopes are spatially close to each other when present on the same molecule. The mutual inhibition pattern and the absence of the 164 epitope from the 231+ cells of a few leukemia patients suggest, however, that 231 and 164 epitopes are not invariably present together. Most DR-positive cells possess 231+ and 164+ and 231+ 164- class II molecules in approximately a 2:1 ratio. This has been confirmed by immune depletion studies. Thus DA6.231 appears to define a supralocus epitope. The 164 epitope may be a marker for a subset of class II molecules exhibiting differential expression on various cell types immortalized by malignant transformation.

Antibodies, Monoclonal↗
PubMed1982

Influence of monoclonal anti-Ia like antibodies on activation of human lymphocytes.

Four monoclonal antibodies directed against human DR antigens were examined for their effects on lymphocyte activation in vitro. Two (DA6.121 and DA6.231) were serologically and biochemically indistinguishable and recognized a common determinant on the DR beta chain. One, DA6.164, reacted with an epitope probably on the beta chain of a subset of DR molecules while the fourth, DA6.147 was directed against an alpha chain determinant. All four produced measurable inhibition of lymphocyte activation. Responses to PHA or PWM were generally reduced by less than 30% and those to autochthonous or to allogeneic lymphoid cells by more than 30% some being completely abolished. DA6.121 and 231 were the most consistently effective antibodies and behaved in an identical manner. There was no additive effect when different monoclonal reagents were mixed. Reduction in the level of activation occurred when the responding population consisted almost entirely of T lymphocytes, suggesting that ADCC was not involved. The presence or absence of complement had a profound effect on the level of lymphocyte mitogenesis but responses were depressed by anti-DR monoclonals under both conditions. The results indicate that both the alpha and the beta chain of DR play some part in lymphocyte activation. It is suggested that the continuous regeneration of DR antigens on the surface of stimulator cells may be important in eliciting MLR.

Adult↗
PubMed1981

Circulating immune complexes and autoantibodies in lung cancer.

The sera of 80 newly diagnosed lung-cancer patients have been examined for immune complexes and autoantibodies. Control subjects consisted of 20 bronchitic patients and 150 normal blood donors. Immune-complex measurements used 4 established and sensitive techniques (Raji cell assay, fluid and solid-phase C1q assays and conglutinin-binding assay) and a 5th newly devised technique based on the binding of polyethylene-glycol-precipitated immune-complex-rich serum fractions to Staphylococcus aureus. Using the Raji cell assay and the S. aureus binding assay to measure immune complexes, both newly diagnosed lung cancer patients and bronchitic patients had significantly higher prevalences of immune complexes than normal controls, but the two groups of patients did not differ significantly in either prevalence or quantity of immune complexes. When techniques which depend solely upon complement fixation (C1q assays and conglutinin binding) were used, only meagre quantities of immune complexes were found, and in at most 15% of newly diagnosed lung-cancer patients. The presence of autoantibodies in newly diagnosed cancer patients and controls appeared to correlate with the increase in the detectable prevalence of immune complexes.

Adolescent↗
PubMed1981

The detection of circulating immune complexes in normal subjects using four different methods.

336 estimations of circulating immune complexes have been performed on the sera of blood donors by four different methods: the solid phase C1q binding test, the fluid phase C1q binding assay, the conglutinin binding test and the Raji cell radio-immune assay. Between 68 and 105 subjects were used in the analysis of each method. With the first three methods, immune complex levels showed a peaked asymmetric distribution with a positive tail including about 10% of subjects, whereas using the fourth method immune complex values were widely spread. No difference in immune complex values between males and females was found. There was a significant trend for the prevalence of immune complexes to increase with age when methods were used which detect complexes through C3 binding. In a further 13 subjects tested at regular intervals during a period of 24 hours, using the fluid phase C1q binding test, significant variations in immune complex levels were found but no consistent pattern of variation at different hours of the day or after meals could be seen. In studies of immune complexes on small groups of patients it is advisable to test multiple samples from te same subjects taken at different times, whereas when large series of patients are being studied results should be compared to those obtained with age matched controls.

Adult↗
PubMed1980

Immune complexes in type I diabetics with persistent islet cell antibodies.

The sera of 33 type I diabetics found to have pancreatic IgG antibodies to the cytoplasm of pancreatic islet cells (ICAb) at three or more years after diagnosis were tested for immune complexes (AgAb), insulin antibodies and thyroid and gastric cytoplasmic antibodies, and the subjects were HLA typed. Sera from 69 insulin treated diabetics of comparable duration of disease and without ICAb at the time of study were also included in the investigation. The prevalence of AgAb in patients with persistent ICAb was found to be 52% in comparison with 19% of ICAb negative diabetics (p < 0.001) and 10% of normal blood donors (p < 0.0005). AgAb positivity was increased, but not significantly, in HLA-B8 positive compared to B8 negative ICAb persisters. There was a significant negative correlation between AgAb levels and insulin antibody titres. Circulating AgAb were not significantly correlated with the presence of either thyroid or gastric cytoplasmic antibodies.

Antibodies↗
PubMed1978

Immune complexes in newly diagnosed insulin-dependent (type I) diabetics.

Soluble immune complexes (AgAb) and islet cell antibodies (ICAb) were studied in 110 insulin dependent diabetics (IDD) within a week of diagnosis and in about a third of the patients after 1, 3, 6 and 12 months. AgAb were studied by the solid phase Clq binding test in all the patients and also by the Raji cell radioimmunoassay in 52 sera at diagnosis. Diabetics at diagnosis showed a significantly higher incidence of AgAb in comparison with the control population. AgAb positivity declined with increasing time from diagnosis to reach the normal range within 3 months. Both the Clq and the Raji methods revealed a significant correlation at diagnosis between the occurrence at AgAb and the presence of ICAb. The possibility exists that AgAb, perhaps comprised of pancreatic antigen and ICAb, may be involved in the pathogenesis of type I diabetes.

Antibodies↗
PubMed1978

Immune complexes and diabetic microangiopathy.

Soluble immune complexes (AgAb) as detected and quantitated by the solid phase Clq assay (Clq-SP) were found to be increased in (a) long-duration diabetics with proliferative retinopathy and (b) short duration diabetics with early onset of retinopathy irrespective of whether they were treated with insulin or oral hypoglycaemic agents (OHA), in comparison to a normal population. No such increases were observed in diabetics of comparable duration without retinopathy. The trend for long-term diabetics to show an increased prevalence of AgAb according to the severity of retinopathy was statistically significant. Detection and quantitation of AgAb by the Raji cell assay (RAJI) gave comparable results although the differences were less pronounced and fell short of statistical significance. AgAb as detected by either method in insulin-treated diabetics could not be correlated with insulin antibodies. These findings suggest that AgAb, not necessarily comprised of insulin and anti-insulin antibodies, may contribute to the pathogenesis of diabetic microangiopathy.

Antibodies↗
PubMed1975

The dominant role of Ia antibodies in the passive enhancement of H-2 incompatible skin grafts.

The ability of H-2 antisera and their constituent K and Ia antibodies to enhance the survival of skin allografts was investigated. Ia sera were prepared from H-2 alloantisera by exhaustive absorption with donor-strain RBC and the absorbed K antibodies were also recovered by acid elution of the RBC. The removal of conventional K/D antibody in no way diminished the activity of enhancing sera over wide dose ranges in two different incompatibility systems. The recovered K/D antibodies in the doses used had at best a trivial enhancing effect. The dominant role of Ia antibodies in enhancement was confirmed by showing significant prolongation of graft survival in third-party systems where the sera covered only some of the Ia antigens in incompatibilities involving K,D and Ia differences and in homologous systems using Ia sera fractionated into their constituent mono-specificities. It is concluded that enhancement is a function of antibodies directed against Ia antigens (I region products) and that antibody against conventional histocompatibility antigens such as H-2.K, D, and by homology HL-A and Ag-B has only a minor role in passive enhancement.

Absorption↗