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S Ferrone

Publications and source records attributed to S Ferrone.

At least 235 records · Page 13Linked to original sources

Antibody-induced association between discrete regions of HLA class I and II antigens.

The anti-HLA-DR + DP monoclonal antibody (MoAb) CR11-462 was unexpectedly found to cross-inhibit the binding to B lymphoid cells of the anti-HLA Class I MoAb CR10-215 and CR11-115. The latter two antibodies recognized the same or spatially close antigenic determinant. The cross-blocking of anti-HLA Class I MoAb CR10-215 and CR11-115 by MoAb CR11-462 reflects neither its contamination by anti-HLA Class I antibodies nor its cross-reactivity with HLA Class I antigens. On the other hand, the cross-blocking appears to reflect redistribution of HLA Class II antigens by the MoAb CR11-462, since the MoAb CR10-215 and CR11-115 are not susceptible to blocking when lymphoid cells are treated with 0.025% glutaraldehyde or are coated with Fab' fragments of the MoAb CR11-462. Furthermore, immunoprecipitates from B lymphoid cells preincubated with the MoAb CR11-462 before solubilization contain HLA Class I antigens. Therefore, these results have shown for the first time an antibody-induced association between discrete regions of HLA Class I and Class II antigens on the membrane of B lymphoid cells.

Antibodies, Monoclonal↗

Analysis with monoclonal antibodies of the molecular and cellular heterogeneity of human high molecular weight melanoma associated antigen.

Monoclonal antibodies (MoAbs) 225.28, 657.9, and 902.5 recognizing distinct epitopes of the human high molecular weight melanoma associated antigen (HMW-MAA) were used to investigate the molecular and cellular heterogeneity of the HMW-MAA synthesized by human melanoma cells. Sequential immunodepletion and immunoprecipitation experiments showed that not all HMW-MAA molecules synthesized by a melanoma cell line express the antigenic determinants recognized by the three monoclonal antibodies. The majority of the HMW-MAA molecules expressed the epitope defined by MoAb 657.9 since this monoclonal antibody depleted the melanoma cell lysate of all antigen molecules recognized by the other two monoclonal antibodies. Depletion with MoAb 902.5 resulted in the removal of a large proportion of the HMW-MAA molecules precipitated by MoAb 657.9. The MoAb 225.28 depleted the cell lysate of only a fraction of the HMW-MAA molecules recognized by MoAb 657.9 and 902.5. Two-dimensional gel electrophoresis and peptide mapping analysis did not detect any significant difference among the HMW-MAA immunoprecipitated by the three monoclonal antibodies. The heterogeneity of the epitopes recognized by the three monoclonal antibodies is, at least partly, due to glycosylation of the antigen molecule, since treatment of melanoma cells with glycosidases differentially affects their ability to bind the three anti-HMW-MAA monoclonal antibodies. Fluorescent activated cell sorting analysis of the melanoma cells showed that the heterogeneity exhibited by the HMW-MAA is not due to the presence of different cell clones in the culture but reflects a differential distribution of epitopes on the HMW-MAA expressed on the surface of individual cells. Immunohistochemical staining of surgically removed benign and malignant lesions of melanocytic origin, of normal tissues, and of malignant lesions has shown a differential tissue distribution of the determinants recognized by the three monoclonal antibodies. Staining of melanoma cell lines and of surgically removed melanoma lesions with combinations of the three monoclonal antibodies did not cause any significant change of the percentage of stained cells but markedly increased the intensity of staining. These results indicate that combinations of monoclonal antibodies to distinct determinants of HMW-MAA can markedly increase the sensitivity of immunohistochemical techniques to detect melanoma cells.

Antibodies, Monoclonal↗

Syngeneic anti-idiotypic antisera to murine monoclonal antibodies to monomorphic and polymorphic determinants of HLA class I antigens.

BALB/c mice were immunized with syngeneic anti-HLA class I monoclonal antibodies. The latter included the anti-HLA-A2, A28 monoclonal antibody (MoAb) CR11-351, the MoAb Q6/64 to a determinant restricted to HLA-B antigens and the MoAb CR10-215 and CR11-115 to the same (or spatially close) monomorphic determinant. Anti-idiotypic antibodies could be detected in bleedings obtained 3 days after the first booster, increased in titer in bleedings obtained after the second booster, and persisted at high levels in subsequent bleedings. The four anti-HLA class I MoAb did not differ in their ability to elicit syngeneic anti-idiotypic antibodies. Cross-blocking studies with a panel of anti-HLA class I, anti-HLA class II, and anti-human melanoma-associated antigen (MAA) MoAb showed that the anti-MoAb CR10-215 and anti-MoAb CR11-115 antisera contain only antibodies to private idiotopes, whereas the anti-HLA MoAb CR11-351 and anti-MoAb Q6/64 antisera also contain antibodies to public idiotopes. The latter are expressed by the anti-HLA class I MoAb CR11-351, Q1/28, Q6/64, and 6/31, and by the anti-HLA class II MoAb Q5/6, Q5/13, 127, and 441. Public idiotopes were not detected on the nine anti-MAA MoAb tested. Public idiotopes do not interfere with the binding of anti-HLA MoAb with the corresponding antigenic determinants. On the other hand private idiotopes are located within the antigen-combining site, because anti-idiotypic antisera specifically inhibit the binding of the corresponding immunizing anti-HLA class I MoAb to cultured human lymphoid cells in a dose-dependent manner. Analysis by isoelectric focusing of the anti-HLA class I MoAb antisera showed that the spectrotype of the anti-MoAb CR11-351 antiserum comprises four components that focus in the pH 6.9 to 6.2 range, the spectrotype of anti-MoAb Q6/64 antiserum comprises three components that focus in the pH 6.5 to 6.1 range, the spectrotype of the anti-MoAb CR10-215 antiserum comprises three components that focus in the pH 6.4 to 6.1 range, and the spectrotype of the anti-MoAb CR11-115 antiserum comprises three components that focus in the pH 6.6 to 6.4 range.

Animals↗

Immunochemical and functional analysis of HLA class II antigens induced by recombinant immune interferon on normal epidermal melanocytes.

The effect of recombinant immune interferon (IFN-gamma) on the expression and shedding of HLA antigens and of melanoma-associated antigens (MAA) by epidermal melanocytes was investigated by using serologic and immunochemical techniques. IFN-gamma enhances the expression and/or shedding of HLA class I antigens and of the cytoplasmic MAA defined by monoclonal antibody (MoAb) 465.12S and induces a slight reduction in the expression of the high m.w. melanoma-associated antigen (HMW-MAA). In agreement with the data in the literature, melanocytes incubated with IFN-gamma acquire HLA-DR, -DQ, and -DP antigens. Contrary to previous information in the literature, the effect is not restricted to HLA class II antigens, since IFN-gamma also induces the expression of the 96-kDa MAA recognized by MoAb CL203. The effect of IFN-gamma on HLA class II antigens and 96-kDa MAA is dose and time dependent and is specific, because recombinant leukocyte interferon affects the expression of neither type of antigen. In spite of the expression of HLA class II antigens, IFN-gamma-treated melanocytes do not acquire the ability to stimulate the proliferation of allogeneic lymphocytes. HLA-DR antigens are more susceptible to induction by IFN-gamma than HLA-DQ and -DP antigens, since the percentage of melanocytes acquiring HLA-DQ and -DP antigens is lower than that acquiring HLA-DR antigens. Furthermore, the dose of IFN-gamma is higher and the time of incubation is longer to induce HLA-DQ and -DP antigens than to induce HLA-DR antigens. The differential susceptibility of HLA-DR, -DQ, and -DP antigens as well as of melanocytes from various donors to the modulating effect of IFN-gamma may provide an explanation for the more frequent detection of HLA-DR than of HLA-DQ and -DP antigens in melanoma lesions and for the expression of HLA class II antigens by some, but not all, melanoma lesions.

Animals↗

Immunohistochemical detection of antigen in human primary and metastatic melanomas by the monoclonal antibody 140.240 and its possible prognostic significance.

An indirect immunofluorescence technique was used to study the tissue distribution of the epitope recognized by the monoclonal antibody 140.240 which identifies a p97-like melanoma-associated oncofetal antigen. Cryostat sections of various normal and neoplastic human tissues were examined. The presence of antigenic activity was demonstrated in 20 of 39 (51%) primary skin melanomas, in 21 of 52 (40%) metastatic melanomas, and in 20 of 44 (45%) nevi. The reactive nevi were restricted to intradermal, junctional, compound and spindle cell types. Of the 110 samples of 12 major tumor types other than melanoma tested, only 1 of 6 epidermoid tumors, 1 of 4 benign breast tumors and 1 of 5 prostatic tumors gave weak staining. This antibody also reacted with sweat glands and fetal small intestine tissue, but not with other adult or fetal normal tissues. Intrapatient as well as interpatient heterogeneity in the epitope expression was present in primary as well as metastatic tumor lesions surgically removed from patients with melanoma. Evaluation of the immunohistologic data and the clinical outcome of patients with melanoma reveals that the expression of the epitope recognized by this antibody is associated with a more favorable prognosis.

Antibodies, Monoclonal↗

Inhibition by anti-HLA class II monoclonal antibodies of monocyte-dependent T cell proliferation induced by monoclonal antibody OKT3.

The inhibitory effect of monoclonal antibodies (mAb) to monomorphic (locus-restricted and locus-shared) and polymorphic determinants of HLA class II antigens on the monocyte-dependent proliferation of T cells stimulated with mAb OKT3 has been studied. The effect appears to be specific, dose dependent, is not mediated by the Fc portion of mAb and reflects their interaction with the corresponding determinants. The anti-HLA class II mAb do not have to be present in the culture throughout the incubation period, but are essential in early phases of mAb OKT3 T cell activation. Both monocytes and T cells are the targets of the inhibition exerted by the anti-HLA class II mAb. Their inhibitory effect involves several steps in the sequence of events which leads to T cell proliferation, including interleukin (IL) 1 and 2 secretion, and IL2 receptor expression.

Antibodies, Monoclonal↗

Role of HLA class I and class II antigens in activation and differentiation of B cells.

The monoclonal antibodies (MoAb) CR10-214, CR11-115, and Q1/28 to distinct monomorphic determinants of HLA class I antigens, the MoAb CL413 and PTF29.12 recognizing monomorphic determinants of HLA-DR antigens, the anti-HLA-DQw1 MoAb KS11, the anti-HLA-DPw1 MoAb B7/21, and the anti-HLA-DR,DP MoAb CR11-462 were tested for their ability to modulate human B-lymphocyte proliferation and maturation to IgM-forming cells. Purified tonsillar B cells were stimulated with Staphylococcus aureus bacteria of the Cowan first strain (SAC) or anti-human mu-chain xenoantibodies, as well as in growth factor- or T-cell-dependent activation cultures. The B-cell proliferative responses induced by SAC or by mitogenic concentrations of anti-mu-chain xenoantibodies were inhibited by some of the anti-HLA class I and anti-HLA class II monoclonal antibodies tested. The same antibodies were effective inhibitors of the proliferation of B cells stimulated with interferon-gamma (IFN-gamma) or interleukin-2 (IL-2) and with submitogenic concentrations of anti-mu-chain xenoantibodies. The proliferation induced by IL-2 of SAC-preactivated B cells was inhibited by some of the anti-HLA class II monoclonal antibodies, but not by the anti-HLA class I monoclonal antibodies tested. This inhibition appeared to reflect at least in part a direct effect on later events of the B-cell activation cascade, since some anti-HLA class II monoclonal antibodies still exerted considerable inhibitory activity when added together with IL-2 to SAC-preactivated B cells after the third day of culture. Anti HLA-DR, DQ, and DP monoclonal antibodies consistently inhibited the IgM production induced in B cells by T cells alone, T cells plus pokeweed mitogen (PWM), SAC plus IL-2, or IL-2 alone. In contrast, two of the three anti-HLA class I monoclonal antibodies tested inhibited the IgM production in cultures stimulated with SAC plus IL-2 and one the IgM production induced by IL-2 alone, but none of them had inhibitory effects on T-cell dependent IgM production. The results reported herein indicate that HLA class II molecules directly participate in different phases of the B-cell activation cascade. In addition, our data also suggest that HLA class I molecules can be involved in the events leading to B-cell proliferation and differentiation into immunoglobulin-secreting cells.

Antibodies, Monoclonal↗

A double determinant immunoassay for HLA class I typing using serum as an antigen source.

We have applied a double determinant immunoassay (DDIA) to HLA-A2,A28, and B13 typing, using serum as an antigen source. The results obtained show a correlation of 96% (B13) and 89.1% (A2,A28) with the results obtained by conventional HLA typing. Furthermore, the results obtained were highly reproducible, since testing of 18 sera on two occasions gave concordant results with all samples tested. The variation in the content of HLA-A2 antigens in sera taken at different times from a given donor was less than 5%. A sevenfold variation was found in the serum level of HLA-A2,A28 antigens: the highest level was found in the sera from HLA-A2,A28 donors and in decreasing order in HLA-A2 homozygous, HLA-A28 homozygous, HLA-A2 heterozygous, and HLA-A28 heterozygous donors. The results of this study indicate that the DDIA is a sensitive, simple, and reproducible procedure for HLA class I typing. The DDIA offers the following advantages in comparison with the conventional lymphocytotoxic assay: it provides information not only about the expression of a given alloantigen, but also about its level; it does not require viable cells, thus facilitating retrospective studies and typing of leucopenic patients; it eliminates variability of results caused by abnormal susceptibility of target cells to complement-dependent lysis.

Antibodies, Monoclonal↗

HLA antigens in colorectal tumours--low expression of HLA class I antigens in mucinous colorectal carcinomas.

Expression of HLA antigens and beta 2-microglobulin was studied by immunoperoxidase staining of frozen sections of 9 mucinous and 10 nonmucinous colorectal adenocarcinomas, 1 cloacogenic carcinoma, 12 colorectal adenomas and 4 samples of normal colorectal mucosa using monoclonal antibodies (MAbs). Staining results were related to histopathological features. HLA Class I antigens were strongly expressed in morphologically normal colorectal epithelium, in all adenomas tested and in all non-mucinous carcinomas. In contrast, expression of HLA class I antigens by the majority of tumour cells was present in only 2 of the 9 mucinous carcinomas, whereas 2 of these mucinous carcinomas were completely negative. In the mucinous carcinomas a striking scarcity of mononuclear inflammatory infiltrate, especially around the mucus accumulations, was observed. HLA class II antigen expression was not detected in normal epithelium and was only focally present in 1 of the 12 adenomas. In 6 out of the 20 carcinomas tested between 20% and 90% of the tumour cells were stained by MAbs against HLA class II antigens. Apart from the low expression of HLA class I antigens in mucinous carcinomas no relationship was found between expression of HLA antigens and histological features of the tumours. The relative poor prognosis of mucinous colorectal carcinoma as reported in the literature may be associated with low expression of HLA class I antigens and scant mononuclear inflammatory infiltrate, which may be a reflection of a weak immune response to the tumour cells.

Adenocarcinoma↗

Differential expression of HLA-DR allospecificities on antigen specific T cell clones.

Serological and immunochemical analysis of T cell clones generated from an HLA-DR3, DR7 donor detected a lower expression of HLA-DR3 than of HLA-DR7 antigen. The defect in the expression of HLA-DR3 antigen appears to reflect abnormalities in regulatory mechanism(s), since the cell surface expression of this antigen could be increased by infecting T cell clones with human T lymphotropic virus I. This finding was paralleled by an increase in the level of mRNA encoded by the HLA-DR beta gene.

Antibodies, Monoclonal↗

Major histocompatibility antigen expression in the liver in acquired immunodeficiency syndrome.

Human leukocyte antigen (HLA) class I molecules are normally detected on most nucleated cells, but not on hepatocytes, while the expression of HLA class II antigens is mainly restricted to certain cell types of the immune system. This normal distribution pattern may be altered in human liver in a variety of disorders, particularly in infectious and immune diseases. In view of multiple infections and severe immune alterations in acquired immunodeficiency syndrome (AIDS), we studied the expression of HLA class I and class II antigens in liver obtained at autopsy from ten patients with AIDS and eight control patients, using a panel of monoclonal antibodies and the indirect immunofluorescence method. In spite of viral bacterial, and fungal infections, HLA class I antigens were detected on hepatocytes in only two patients with AIDS. Human leukocyte antigen class II antigens were found unexpectedly on bile duct epithelium in five of ten patients with AIDS and in one of eight control patients. The aberrant HLA class II antigen expression on bile ducts does not appear to be linked to bile duct damage or infection with cytomegalovirus or other agents, but may be related to immune alterations in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

A sandwich assay to detect and characterize syngeneic anti-idiotypic antibodies to murine anti-HLA and tumor associated antigen monoclonal antibodies.

The parameters of a sandwich assay to analyze syngeneic polyclonal and monoclonal anti-idiotypic antibodies to murine anti-HLA and anti-human melanoma associated antigen monoclonal antibodies have been characterized. Furthermore, the sensitivity of the sandwich assay has been compared with that of assays widely used to characterize anti-idiotypic antibodies, i.e., the binding assay to F(ab')2 fragments of monoclonal antibodies and the radioimmunoassay. The latter is more sensitive than the sandwich assay when monoclonal anti-idiotypic antibodies are tested, but less sensitive when anti-idiotypic antisera are analyzed. Both assays are less sensitive than the binding assay to F(ab')2 fragments of monoclonal antibodies.

Animals↗

Cellular immune response to human sarcomas: cytotoxic T cell clones reactive with autologous sarcomas. I. Development, phenotype, and specificity.

Human T cell clones cytotoxic for autologous sarcoma cell lines have been developed from patient JM with an osteogenic sarcoma, and from patients EG and RM with malignant fibrohistiocytoma. These clones were derived from the cocultivation of peripheral blood lymphocytes (PBL) with the respective patient's autologous irradiated established tumor cell lines (AIT). After two cycles of stimulation for 5 days in bulk culture, these "educated" lymphocytes were seeded at a density of 1 X 10(6) cells/well in 24-well plates and were cultured in the presence of highly purified natural IL 2 and AIT, the latter serving as a feeder layer. Cell numbers were reduced from the initial seeding density by one log each week until reaching a density of 10(2) cells. These cells were found to be stable in viability and cytotoxic activity, after which limiting dilution was then performed. Within 4 to 6 wk, clones were isolated with unique specificities. These clones were capable of proliferating to a total density of 10(9) cells/ml and maintained their specific cytotoxicity for more than 6 mo. Testing with a panel of target cells of various histotypes, cold-target inhibition assays, and blocking of cytotoxicity with anti-HLA monoclonal antibodies showed that the T cell clones recognize a common sarcoma-associated antigen and that the lysis is HLA restricted. Phenotypically, cytotoxic clones derived from JM were Leu-1+, Leu-2+, and Leu-3-, whereas those derived from EG exhibited either Leu-24 or Leu-3+ markers, the latter phenotype lacking cytotoxicity. RM exhibited mainly Leu-3+ clones with strong cytotoxicity. All were HNK-1- and HLA class II+, with less than 1% of cells of each clone stained by anti-TAC monoclonal antibody. The clones from each patient did not lyse autologous or allogeneic PBL, mitogen-induced T lymphoblasts, normal fibroblasts, cells isolated from benign neoplasms, carcinoma cells, Daudi B lymphoid cells, or K562 cells. With the exception of EG, all clones produced immune interferon in a range from 12 to 50 U/ml. The generation of long-term specific T cell clones can be used to further dissect the cellular immune response to sarcomas. Cytotoxic T cell clones have potential application for tumor immunotherapy.

Antigens, Neoplasm↗

T cells from patients with chronic liver diseases: abnormalities in PHA-induced expression of HLA class II antigens and in autologous mixed-lymphocyte reactions.

The expression of HLA Class II antigens by resting and phytohemagglutinin (PHA)-activated T cells and their functional properties in autologous mixed-lymphocyte reactions (MLR) were investigated in patients with chronic active hepatitis, with alcoholic cirrhosis, and with primary biliary cirrhosis. In all groups of patients the percentage of resting T cells expressing HLA Class II antigens was significantly higher than that in controls. The percentage of T cells which acquired HLA Class II antigens following PHA stimulation was reduced in patients with chronic active hepatitis, serum hepatitis B surface antigen (HBsAg) positive, and in those with alcoholic cirrhosis, HBsAg negative, although the level of [3H] thymidine incorporation was within normal limits. The degree of proliferation in autologous MLR with PHA-T cells was significantly reduced in patients with chronic active hepatitis, HBsAb positive, and in those with alcoholic cirrhosis, HBsAg positive. A reduced proliferation was also detected in autologous MLR with non-T cells, in patients with chronic active hepatitis, HBsAg positive. The abnormalities of autologous MLR are selective, since the proliferative and stimulatory activities of cells from patients with chronic liver diseases in allogeneic MLR were within normal ranges. The immunoregulatory role of HLA Class II antigens and of autologous MLR suggests that the abnormalities we have identified may play a role in the immunological dysfunctions underlying chronic liver diseases.

Adult↗

Autologous B lymphoblastoid cell lines and long-term cultured T cells as stimulators in the mixed lymphocyte reaction: analysis of the role of HLA class II antigens as stimulatory molecules.

Human activated T cells, long-term cultured in the presence of interleukin 2 (IL 2), were compared with autologous Epstein Barr virus-transformed B lymphoblastoid cell lines for expression of human leukocyte (HLA)-HLA-DR and -DQ antigens and for ability to induce proliferative responses in autologous and allogeneic lymphocytes. Immunofluorescence analysis performed with a panel of monoclonal antibodies (mAb) specific for HLA-DR or -DQ antigens did not reveal any significant difference in the expression of HLA-DR antigens but revealed reduced expression of HLA-DQ antigens on two out of four T cell lines tested. No obvious difference could be detected in the two-dimensional gel electrophoretic profile of HLA-DR and -DQ beta-chains synthesized by the autologous pairs of B and T cell lines. In contrast with previous reports, the IL 2-dependent cell lines consistently induced alloproliferative responses in standard 6-day mixed lymphocyte cultures; however, these responses were severalfold lower than those elicited by the autologous B lymphoid lines. Both anti-HLA-DR and anti-HLA-DQ mAb blocked the proliferative responses induced by the B cell lines but did not affect those generated by the T cell lines, suggesting that the latter cells induce T lymphocyte activation via a mechanism independent of HLA-DR or -DQ antigen expression on their surface. Addition of IL 2 to the mixed cultures with B cell lines as stimulators did not affect the outcome of the proliferative responses but partially or completely reversed the blocking activity of the mAb. In contrast, IL 2 significantly enhanced the alloproliferation induced by the T lymphoblastoid cell lines, and the anti-HLA class II mAb partially antagonized this effect. Taken together, these data suggest that unlike the HLA-DR and -DQ gene products on B cells, those on IL 2-dependent long-term cultured T cells do not play a direct or primary stimulatory role in the mixed lymphocyte reaction; the reduced levels of alloproliferation induced by the T cell lines are, at least in part, due to a defective production of endogenous IL 2 by the responder lymphocytes rather than to a defective expression of IL 2 receptors by the alloproliferative T cell subset; and the anti-HLA class II mAb in these cultures act only at the responder cell level, since they can efficiently block the enhancement of T cell proliferation triggered by exogenous IL 2, but not the proliferative responses induced by T cell lines in standard conditions.

Antibodies, Monoclonal↗

The monoclonal antibody CJA3 down-regulates the susceptibility of human tumor cell lines to natural cell-mediated cytotoxicity.

While developing monoclonal antibodies (MoAb) to colorectal carcinoma (CRC) cells, we noted that one MoAb, termed CJA3, down-regulated natural cell-mediated cytotoxicity (NCMC) against CRC cell lines SW480 and SW620. The MoAb CJA3 was developed by immunizing a BALB/c mouse with fresh human colorectal adenocarcinoma cells. The antigen recognized by the MoAb CJA3 was expressed on several solid tumor cell lines and on one of the six lymphoreticular cell lines tested, but was not detected on normal peripheral blood lymphocytes (PBL). SDS-PAGE analysis of the antigen immunoprecipitated by the MoAb CJA3 from the CRC cell lines SW480 and SW620 and from the melanoma cell line MALME-3M revealed a component with a m.w. of 150,000. Preincubation of CRC cell lines SW480 and SW620 with the MoAb CJA3 for 16 hr reduced their susceptibility to NCMC by about 50%. Kinetic experiments showed that prolongation of the incubation of target cells with the MoAb CJA3 resulted in a time-dependent increase in the amount of MoAb bound. Maximum binding of the MoAb CJA3 was reached after 4 hr of incubation. The increase in antigen expression chronologically paralleled the decrease in NCMC target cell sensitivity, suggesting that the membrane alterations induced by the MoAb CJA3 were important for NCMC against these two cell lines.

Antibodies, Monoclonal↗

Associated expression of HLA class I and class II antigens on melanoma cells in surgically removed metastases.

Malignant transformation of melanocytes and further neoplastic progression may be associated with qualitative and/or quantitative changes in expression of HLA class I and class II antigens. Since previous immunohistochemical studies of surgically removed melanoma lesions have suggested a relationship in the expression of HLA class I and class II antigens, we have investigated the expression of these antigens at the single cell level. Double immunofluorescence staining of frozen sections of melanoma metastases and immunoelectron microscopic double labelling of melanoma cell suspensions prepared from three of these lesions has detected three HLA phenotypes on the large majority of melanoma cells: either both HLA class I and class II antigens, neither HLA antigen or only HLA class I antigens. In four out of the 11 lesions a few melanoma cells were found to express HLA class II antigens and to lack HLA class I antigens. A relationship was also found in the level of expression of HLA class I and class II antigens, as estimated by the intensity of staining with monoclonal antibodies. The level of expression of HLA class II antigens appeared to be similar to or lower than that of HLA class I antigens on the large majority of melanoma cells. This coordinated heterogeneity in the expression of HLA class I and class II antigens by melanoma cells may have implications in the interactions of tumour cells with the host's immune system.

Fluorescent Antibody Technique↗

Abnormalities of T cells isolated from mediastinal lymph nodes and peripheral blood of patients with lung carcinoma: deficit in PHA-induced expression of HLA class II antigens and in autologous mixed lymphocyte reactions.

A reduced percentage of T cells isolated from mediastinal lymph nodes and peripheral blood of patients with lung carcinoma acquired HLA Class II antigens following in vitro stimulation with PHA. Furthermore T cells were functionally abnormal in autologous and allogeneic mixed lymphocyte reactions (MLR). The immunoregulatory properties of HLA Class II antigens and autologous MLRs suggest that these abnormalities may affect the interaction of the host's immune system with tumor cells.

Adult↗