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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that lymphocytes from renal allografted patients with a good functioning graft display donor-specific cell-mediated lympholysis nonreactivity (CML-NR) in vitro. To define whether the HLA system influences the occurrence of the CML-NR, immunogenetic studies were carried out. Posttransplant lymphocytes derived from CML-NR patients were stimulated in vitro with lymphocytes from unrelated healthy blood donors, who were selected for the presence or absence of kidney donor-specific HLA antigens. The presentation of kidney donor-specific HLA-B (and -C) antigens on the lymphocytes of unrelated blood donors resulted in cytolytic nonresponsiveness, whereas presentation of the kidney donor-specific HLA-A locus antigens on lymphocytes of the unrelated blood donors revealed no cytolytic nonresponsiveness. The results, as displayed by posttransplant lymphocytes of renal allografted patients, demonstrate that the kidney donor HLA-B (and -C) antigens are responsible for the in vitro-observed, donor-specific CML-NR. Consequently, presentation of cells from panel members matched to the kidney donor at the HLA-B locus suppresses the response towards HLA-A locus antigens. The in vitro-observed cytolytic nonresponsiveness appeared not to be due to an absence of specific cytotoxic T lymphocytes, because the nonresponsiveness can be abrogated by addition of exogenous IL 2.
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PMID:HLA regulates postrenal transplant CML nonreactivity. 390 Feb 3

Human CTL that recognized MHC-controlled determinants distinct from HLA-A. B, C, and D/DR antigens were tested in a family with nine siblings. Segregation analysis of positive CML reactions showed strong lysis of target cells of three HLA-identical siblings, inheriting the b and c MHC haplotypes (blc), but not of the parents or siblings inheriting only one of these haplotypes. Some cytotoxicity was seen against parental target cells, although it seemed to be qualitatively distinct from that directed against the b/c targets. Studies using the competitive inhibition technique showed that cells inheriting only the b or c haplotypes were not effective in decreasing the specific cytotoxicity. Furthermore, simultaneous inclusion of inhibitor cells of both the b and c haplotypes did not hinder the specific cytotoxicity. Induction of CTL recognizing this new determinant did not occur when either antigens of the b or c haplotypes were used as MLC stimulating cells, or when antigens of both haplotypes were presented simultaneously, but on separate stimulating cells, in a three-cell MLC. These results suggest that the target determinant recognized by these unusual CTL is complex; it may be formed through interactions of two surface molecules or by genetic complementation yielding a hybrid antigen.
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PMID:Noncodominant expression of target antigens recognized by human cytotoxic T lymphocytes. 616 57

Five sets of cytotoxic effector cells were generated, using haplo-identical, first degree relatives in five different families, against the HLA-A3; B7 serological determinants combined with different DR antigens. When tested against a panel of cells bearing combinations of the HLA-A, -B and -DR antigens it was shown that the HLA-B7 antigen was as strong a CML target determinant alone as it was in the presence of HLA-A3. The strength of the HLA-A3 antigen as target determinant varied. With effector cells primed to the HLA-A3; B7; DR2 haplotype, the A3 antigen alone behaved as a weak target determinant. When the same target cells were tested with the effector cells generated against HLA-A3; B7 without DR2, the A3 antigen behaved as a strong target determinant. A number of target cells lacking the serologically detectable HLA determinants present on the sensitizing HLA haplotype were identified as being killed by specific effector cells. These data suggest either a number of new CML target determinants controlled by different loci or the presence of a single, new locus with multiple alleles controlling CML targets.
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PMID:Differential behavior of cytotoxic effector cells against HLA antigens in strong genetic linkage disequilibrium. 616 80

Class I antigens were isolated by immunoprecipitation from cell extracts prepared from mitogenically stimulated and internally radiolabeled peripheral blood lymphocytes (PLBs). The precipitating antibodies used are monomorphic and recognize a determinant on the heavy chain of HLA-A, B, C antigens regardless of their allelic specificities when complexed with beta 2m, or determinants on beta 2m itself. Comparison of class I molecules isolated from 25 different homozygous typing cells (HTC) and analyzed by two-dimensional (2-D) gel electrophoresis allowed the identification of those HLA-A, B locus specificities most common in the European Caucasoid population. Class I antigens isolated from HTC that are HLA identical are biochemically indistinguishable also. Evidence was obtained for the expression of additional class I antigens besides the HLA-A, B, C locus products: for some haplotypes, up to six class I genes may be active in mitogenically activated PBLs.No differences in molecular weight and isoelectric point of the class I heavy chains were observed between the antigens recognized by W6/32, the anti-heavy chain reagent, and anti beta 2m reagents. The nature of the mitogenic stimulus, i.e., pokeweed mitogen or phytohemagglutinin, was irrelevant with respect to the class I antigens isolated by this method. Using the HTCs as reference, a panel of HLA-B27 positive heterozygous cells was analyzed. Two types of HLA-B27 antigens, distinct by CML typing were represented. These two forms differed also in their biochemical properties. In addition, we obtained evidence for the existence of an A2 variant. This finding was likewise confirmed by CML typing.
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PMID:Analysis of human class I antigens by two-dimensional gel electrophoresis. I. Polymorphism, evidence for additional (non-HLA-A, B, C) gene products, and identification of variant HLA-A, B antigens. 618 77

Some CTLs recognize HLA-structures in a different way than antibodies, i.e. they may identify other epitopes than antibodies or may define genetically distinct structures. From population studies, in vitro educated CTLs were selected giving rise to significant lysis on PHA-lymphoblasts in the absence of the sharing of HLA-A, B, (C) determinants between stimulator and target lymphocytes. Based on pair-wise correlations these CTLs form 3 clusters, identifying structures associated to HLA-markers. Subsequent testing in 14 complete families of greater than or equal to 4 children allowed the observations: (1) CML-traits assigned on the basis of single CTLs often segregated in a non-mendelian way or independent of HLA. (2) Assignment made on the basis of CTL-clusters segregated with HLA. (3) in 2 informative HLA-B/D, DR recombinant families, CML-traits segregated with HLA-B. (4) No haplotype could be assigned more than one CML-trait.
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PMID:Typing by cytotoxic lymphocytes. Genetics of HLA-non-A, B, C determinants - family studies. 646 Oct 89

Biochemical analysis of HLA-B27 antigens from individuals that are HLA-ABC identical by serology but distinct in CML typing establishes that two types of HLA-B27 can be defined biochemically. The division of HLA-B27 into a W type and a K type by CML typing correlates perfectly with the biochemical data. HLA-B27 K type possesses a more basic isoelectric point than HLA-B27 W type. Neuraminidase digestions of immunoprecipitated HLA-A,B antigens establish that the difference in isoelectric point between HLA-B27 K and HLA-B27 W is not due to differences in sialic acid content.
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PMID:Biochemical analysis of variant HLA-B27 antigens. 660 Oct 98

This report describes the influence of HLA-D/DR antigen disparity upon the level of cytotoxicity in allogeneic in vitro cultures. Allogeneic cultures, between unrelated HLA-D/-DR full house donors, tested in CML gave three different levels of cytotoxicity, termed weak, intermediate and strong cytotoxicity. HLA-D/-DR compatibility predicts weak cytotoxicity and two HLA-B antigen incompatibility predicts strong cytotoxicity. On the contrary, HLA-A antigens have no major influence upon the strength of cytotoxicity. Accepting that the MLC/CML reaction is an in vitro parallel to the in vivo transplantation of allogeneic tissue, the observations are in accordance with the results of HLA-D/-DR matching for graft survival in human renal transplantation.
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PMID:Influence of HLA-D/DR antigen disparity in CTL generation in vitro. 660 61

D cells are lymphocytes bearing both receptors for the third complement component and the ability to form spontaneous rosettes with SRBC. We report the case of a patient with a D-cell chronic lymphatic leukemia who presented a long evolution without treatment and whose leukemic cell characteristics have been extensively studied. Cytogenetic analysis showed numerous karyotypic abnormalities among leukemic cells; all metaphases were hypodiploid and arranged in four different clones; seven marker chromosomes were present. The cells were found to bear human T-cell specific antigen, the T helper/inducer phenotype, HLA-A and HLA-B determinants, but no HLA-DR antigens. They displayed a high proliferative response to PHA and Con A, no response to PWM stimulation, and possibly the capacity of allogeneic stimulation in the mixed lymphocyte culture system. Assays for cell-mediated cytotoxicity in the CML system, and for K and NK activities were negative.
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PMID:Membrane markers, karyotypic abnormalities, ultrastructure and functional properties of lymphocytes in a case of 'D-cell' chronic lymphatic leukemia. 671 63

The diminished response to secondary stimulation of human lymphocytes primed in bi-directional (BD) mixed lymphocyte culture (MLC) has been demonstrated to be due to cytotoxic destruction of the responder cells by the numerically superior allogeneic stimulating cell population. This phenomenon is called Functional Cell Mediated Lympholysis (F-CML). Matching for HLA-A and B, HLA-DR or for MLC non-responsiveness (HLA-D) in unrelated pairs does not ablate F-CML, indicating that none of these loci serve as the exclusive target for this activity. One locus appears to be centromeric from HLA-A in an A/B recombinant family and a B/D recombinant family demonstrates a target centromeric from HLA-B. A special family with homozygous for HLA-A, B and D provided evidence for an additional locus other than HLA-A, B or D. Thus, genetic studies indicate that at least one target antigen of F-CML may be coded for by a locus that is centromeric from HLA-B and which may be distinct from HLA-D or DR.
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PMID:Functional cell mediated lympholysis: II. Genetics. 694 37

Nine antigens systems were defined. Two were related to HLA-A,B,C and to Ia-like antigens; the others could be grouped into three categories. (i) NL-22, NL-1: NL-22 antibody reacted with leukemia cells from 12 to 16 cases of null cell acute lymphocytic leukemia (null-ALL) but not with any other type of leukemia tested or with lymphoid cells of various origins. Among cultured cell lines tested, one (NALM-6) of three null-ALL cell lines was positive, the others were negative. Absorption analysis confirmed the restriction of NL-22 antigen to null-ALL. NL-1 antibody was reactive with leukemia cells from 10 to 16 cases of null-ALL and 3 of 6 cases of chronic myelocytic leukemia in blastic crisis (CML-BC). The antigen was present also on a minor population of normal lymphoid cells. The distribution and molecular weight (100,000; glycoprotein) of the NL-1 antigen resembled that of the previously described common ALL antigen (cALL). (ii) NL-30, NL-4: Both antibodies exhibited almost identical patterns of reactivities against cultured cell lines tested. They reacted with leukemia cells from some cases of null-ALL, adult T-cell leukemia, and CML-BC, although they showed discordance in their reactivities against a panel of leukemia cells, (iii) NL-9, NL-8, NL-25: These three antibodies detect serologically distinguishable determinants on a broad range of leukemias and normal lymphoid and hematopoietic cell types. The antibodies analyzed in this study provide evidence for the heterogeneity of null-ALL by demonstrating a variety of antigen phenotypes on leukemia cells. One of the antigens (NL-22) appears to be restricted to null-ALL.
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PMID:Serological analysis of cell surface antigens of null cell acute lymphocytic leukemia by mouse monoclonal antibodies. 695 69


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