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Aim Donor-specific antibodies (DSA) are associated with increased cardiac graft loss. Detection of antibody-mediated rejection (AMR) relies on graft dysfunction, C4d immunofluorescence (IF) and DSA. We applied a C1q solid-phase assay in parallel with the standard IgG SAB assay to examine the correlation of circulating complement-fixing donor-specific antibodies and presence of C4d in endomyocardial biopsy (EMB). Methods We retrospectively studied the relationship of C1q+ DSA, and C4d IF in 40 EMB from 38 cases of heart transplant recipients (The Journal of Heart and Lung Transplantation, Vol 32, No 4, April 2013). C4d evaluation was performed for cause, including (1) clinical evidence of graft dysfunction; (2) high PRA; and (3) ACR, ISHLT Grade 3R. We applied a C1q solid-phase assay in parallel with the standard IgG SAB assay to examine the DSA profiles in heart transplant patients post-transplant. The MFI cut off values of IgG DSA and C1q+ DSA are > 1,000 and >200 respectively. Results A better concordance is observed between C1q+ DSA with C4d IF+ as compared to IgG DSA with C4d IF+ (54% vs.24%, p = 0.09, paired samples T test). However, the correlation of C1q DSA with C4d IF is not statistically significant ( p = 0.12, Fisher Exact test). Importantly, C1q+ DSA is observed in 14/15 cases with C4d IF +; 17 cases had circulating C1q+ DSA without detectable C4d staining (Table), suggesting that that the presence of C1q+ DSA may precede the detection of C4d deposition in EMB and/or the development of AMR. [ Table 1 ] Conclusions In this cohort of 38 patients, no significant correlation is observed between circulating C1q DSA and C4d IF in EMB. Additional studies are needed to further evaluate the association of C1q DSA with EMB and IF C4d staining, and with long-term outcomes in heart transplant recipients.

Aim Alloreactivity to pancreatic islet cell transplantation (IT) has been reported previously particularly for those IT recipients with a history of sensitization events prior to transplant. The aim of this CIT Consortium study was to determine the incidence of HLA alloimmunization and characterize donor-specific antibody (DSA) profiles after IT. Methods We conducted a prospective, single-arm, Phase III study of IT alone (CIT-07) in T1D in subjects 18 to 65 years of age in 12 transplant centers. Standardized procedures were used for islet manufacturing, patient selection, immunosuppression (Sirolimus, Tacrolimus, Etanercept, Rabbit ATG), transplantation and care. Anti-HLA antibody screening was performed using multiple solid phase assay platforms including the LABScreen® Single Antigen assay at Day 75, Months 6, 9, 12, 18 and 24 after IT. Analyses of antibody specificity included HLA class I (A, B, C) and class II (DR, DQA, DQB, DP). Subjects with HLA antibodies (MFI > 3,000) or pre-transplant DSA (MFI > 700-1,000) were deemed ineligible. CPRA was calculated using an MFI cut off value of 3,000. DSA was defined as bead reactivity with an absolute MFI > 1,000 and an increase in MFI > 50% when compared to pre-IT reactivity. Results Patients received an initial transplant between October of 2008 and September of 2012 Study follow-up will be complete in May of 2014. 48 subjects were transplanted and followed for at least 24 months. 25 of the 48 subjects received a second transplant and 1 subject received a third transplant. An interim analysis through April of 2013 showed that 3/48 (6%) developed DSA while on IS. The PRA remained negative in all patients without DSA. The follow up period ranged from 364 to 1571 days with a median of 736 days. Conclusions The CIT-07 protocol shows a low incidence of PRA or DSA using standardized procedures for islet manufacturing, patient selection and care, and HLA antibody testing. Future studies should evaluate long-term outcomes after DSA development.

Aim In combined liver kidney (CLK) transplants (Txp), the kidney is not always protected from rejection when pre-Txp donor specific antibodies (DSA) are present. We applied a C1q solid-phase assay to examine complement-fixing DSA in CLK Txps who developed accelerated antibody mediated rejection (AMR). Methods Four CLK Txps who had high PRA and high levels of DSA pre-Txp were evaluated. Pre- and post-Txp sera were analyzed for DSAs using commercially available single-antigen bead assay kits. The MFI cut off values of IgG DSA and C1q+ DSA are >1,000 and >300 respectively. Two of these 4 recipients (case 1 and 2) experienced biopsy-proven AMR during the first 2 weeks post-txp. Results All 4 cases had a persistent Post-Txp IgG DSA (Table). The 2 subjects who developed AMR had very high pre-Txp C1q+ DSA levels (MFI range for single specificity: 10,800-17,500). In contrast, case #3 who had relatively lower pre-Txp C1q DSA (MFI= 4,400) did not experience AMR.[ Table 1 ] Conclusions With the limitation of small number of cases, the presence of high levels of pre-Txp C1q+ DSA appears to be associated with an increased risk of AMR of the kidney. Future studies should evaluate the risk of AMR and long-term outcomes associated with the presence of C1q+ DSA during the pre- and post-Txp periods in CLK Txps.

We report the occurrence of clinically definite multiple sclerosis in an offspring of a couple with conjugal multiple sclerosis. Extensive investigation of all members of this family, which includes two additional asymptomatic children, eliminated the possibility of alternative neurological diagnoses. All family members were studied with magnetic resonance imaging (MRI), evoked potentials, and human leukocyte antigen (HLA) typing. An asymptomatic child had subtle white matter abnormalities on MRI, suggesting subclinical neurological involvement This study documents the third case of multiple sclerosis in the child of conjugal multiple sclerosis patients and provides the first report of MRI lesions in an asymptomatic offspring of the same parents. Neurodiagnostic and immunogenetic investigations of such rare family clusters may contribute to the elucidation of the pathogenesis of multiple sclerosis.

Activated T cells are implicated in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system. Serial measurements of T cell activation molecules and T cell subpopulations were performed over 12 months in patients with chronic progressive multiple sclerosis and healthy controls, and correlated with clinical indices of disease progression measured by standardized disability scores. Of the markers studied, the activation molecule CD26 appeared to exhibit a more consistent pattern and to be elevated in MS patients; therefore we concentrated our attention on this marker, especially in view of recent evidence of its role in T cell activation. In this small patient group, the elevation of CD26 in the MS patients did not reach statistical significance, when compared to the level in the controls. Interestingly, the percentage of CD26 but not CD25 or HLA-DR correlated with the MS patients' disability scores. However, the clinical significance of this observation as an indication of disease activity in chronic progressive MS remains to be demonstrated in studies of larger patient populations.

Aim HLA compatibility is assessed by crossmatching (XM) and donor specific antibody (DSA) testing. Flow cytometric XM (FXM) results vary among centers due to variation in reagents and sample preparation. We evaluated FXM variability and effects of test standardization in 6 US centers participating in the HALT study. Methods 6 labs performed FXM using 3 exchanges (Exch) including sera with weak DSA and either frozen (1) or fresh (2) cells. All samples were sent from 1 lab, which screened sera by single antigen beads and typed cells for HLA-A,B,C,DRB1/3/4/5,DQB1. HLA typing and DSA results were not revealed to the other labs until study completion. FXM data assessed included cell viability, pronase and anti-hIgG concentrations, instrument and channel settings, and fluorescence (FL) values. Four different cytometer types were used by the labs. Labs used their own methods for Exch 1 and 2. In Exch 3, sample preparation and reagents were standardized: pronase (2 mg/ml); anti-hIgG dilution (1:500). Results Each Exch had 10-24 T/B FXM comparisons. Exch 2 (S1 vs C1) was a negative control. Table 1 shows range of variation in FL values. Table 2 shows expected vs observed interpretations. Conclusions The discrepant results produced by varying FXM methods raise concerns about the assessment of HLA compatibility results from multicenter clinical trials. Standardization of reagents and sample preparation improved FXM result concordance among centers demonstrating that standardization can reduce the variation of results often seen in a multicenter clinical trial. Partially funded by the NIH, NHLBI grant R34 HL10541.

Aim Virtual cross matches (VXMs) are key to the success of KPD by aiding identification of compatible donors for sensitized candidates. We evaluated the success of unstandardized VXMs combined with donor preselection by National Kidney Registry (NKR) centers in a population of mostly sensitized and/or ABO incompatible patients. Methods The NKR initiated 437 match offers among 62 US transplant centers based on acceptable VXMs between 3/14/2011 to 3/31/2012. We evaluated the accuracy of the VXM by examining whether or not offers were declined due to positive final XMs. The VXM considered antibodies to HLA-A, B, C, DRB1/3/4/5, DQB1 and DPB1 detected by Single Antigen assays and donor HLA typing. Each center established its own immunological criteria for donor acceptability. To reduce late stage match failures online pre-selection of donors was introduced in July 2011 which allowed centers to accept potential donors based on HLA types and other characteristics prior to a match run. Results NKR centers achieved a 92% VXM accuracy rate and completed 181 transplants; 32% of these had PRA > 80%. Only 29 (8%) offers were rejected by the recipients’ center due to an unacceptable positive final crossmatch. In most cases, the discrepancy with the VXM was due to DSA at or near the center’s threshold or to multiple DSAs when each fell below the threshold of unacceptability. Other cases were due to DQA antibodies (3), non-HLA antibodies (3), a change in antibody profile (1), and data entry error (1). Interestingly, the rate of false negative VXM remained unchanged after the implementation of the pre-selection strategy, while the rate of late-stage cancellations due to unacceptable donors decreased from 5% to 2%. Conclusions Access to transplant for sensitized patients with minimal disruption of chains has improved by pre-selection of acceptable pairs, optimizing data entry for the VXM, frequent antibody monitoring following sensitizing events and good communication between transplant centers and their labs. Sinacore: NKR: Employee.

OBJECTIVE: To report the usefulness of bortezomib therapy in a sensitized lung transplant recipient experiencing antibody-mediated rejection. CASE SUMMARY: During a pretransplant evaluation, a 62-year-old woman with usual interstitial pneumonitis developed a diverticular bleed requiring transfusions, which elevated her panel reactive antibody to 98% for human leukocyte antigen (HLA) class I and 71% for class II. She underwent desensitization to decrease her panel reactive antibody levels. She received a double lung transplant across a weak HLA class II incompatibility but developed respiratory failure due to early graft dysfunction. On postoperative day (POD) 14 she was found to have donor-specific antibodies (DSA) to HLA class I and class II antigens. She received intravenous immunoglobulin (IVIG), plasmapheresis, and bortezomib to reduce the DSA. Repeat DSA testing on POD 80 demonstrated a 50% reduction in DSA, which became undetectable at POD 255. DISCUSSION: Antibody-mediated rejection (AMR) is difficult to diagnose and treat in lung transplantation. Since primary treatment options such as plasmapheresis and IVIG alone may not adequately eradicate DSA, the proteasome inhibitor bortezomib can be of additional value for the treatment of AMR. Bortezomib causes apoptosis of plasma cells, thus eliminating the production of allograftspecific DSA. CONCLUSIONS: This is the first report describing the utility of bortezomib for early graft dysfunction in a highly sensitized lung transplant recipient. Although this patient had preformed donor-specific anti-HLA antibodies, AMR was successfully treated with a combination of plasmapheresis, IVIG, and bortezomib. At time of writing, the patient continued to have excellent graft function 2 years posttransplant. Bortezomib is a potent inhibitor of plasma cell production and it appears to be useful for the treatment of antibody-mediated graft dysfunction.

DNA sequence analysis of DPB1 second exons shows great variability with over 50 alleles. This report describes a new HLA-DPB1 allele present in a Caucasoid donor bearing the class II alleles DRB1*0901/1301, DRB3*0101, DRB4*0101, DQB1*0603/0303, and DPB1*1101. 6 refs., 1 fig.

Tyrosine phosphorylation is thought to be one of the earliest steps in antigenic activation of T cells. Three nonreceptor tyrosine kinases, p56lck, p60fyn, and ZAP-70, are known to be involved in T cell receptor (TCR) signaling, albeit their functional roles appear to be different. Whereas p60fyn and ZAP-70 are functionally associated with the T cell antigen receptor, p56lck is essential for TCR signaling without being directly coupled to the TCR. We have studied a mutant variant of the Jurkat T cell line (J32–3.2), in which basal activities of p56lck and p60fyn are 2- to 2.5-fold reduced relative to those in its parental line (J32) while basal activity of ZAP-70 remains unchanged, and compared responses of J32–3.2 and J32 to TCR stimulation. We have demonstrated that tyrosine phosphorylation following CD3 cross-linking in J32–3.2 cells was extremely short-lived and thus insufficient for the induction of subsequent physiological responses. This was at least partially due to the diminished tyrosine kinase activity in these cells. A decrease in the activity of src-related kinases was caused primarily by their lower expression, whereas expression of ZAP-70 was unchanged but its response to CD3 crosslinking was diminished, correlating with the deficient tyrosine phosphorylation of the CD3 -chain, recently observed in J32–3.2. These data are consistent with the idea that sir-related kinases phosphorylate the -chain, which in turn recruits ZAP-70 required to sustain the signal. J. Leukoc. Biol. 55: 289–298; 1994.

Multiple lymphoid cell lines were derived from 35HLA-D homozygous donors by EB-viral transformation of B lymphocytes. The expression of Ia-like alloantigens (HLA-DR) was studied by microcytotoxicity and by absorption with alloantisera exchanged through the Seventh Histocompatibility Workshop. B-lymphoid lines expressed the same specificities as normal B lymphocytes. Workshop antisera representing DRw1, DRw2, DRw3, and DRw7 gave well-defined typing patterns with cell lines derived from donors of corresponding D-locus specificities. A more complex reaction pattern was seen for antisera representing DRw4, DRw5, and DRw6. The available reagents could not discriminate between lines from donors homozygous for Dw4, Dw10, or D-KH. All lines studied, except for those from one donor homozygous for a unique D-locus determinant (D-SPO), could be assigned one of the provisional DRw specificities. The advantage of obtaining multiple cell lines from a single donor was evident. One line could not be typed by microcytotoxicity because it was lysed in all human sera tested, and some other lines gave weak cytotoxic reactions. Absorption studies, however, did indicate similar expression of DRw antigens on these lines. The availability of multiple lines from the same donor circumvented these difficulties.

The gibbon ape leukemia virus (GaLVSF)-infected T cell line, MLA 144, was established from the lymphoma of a gibbon ape. The cell line constitutively expresses IL-2 and its receptor, implying that an autocrine mechanism could be responsible for or contribute toward its growth. To explore the mechanism of constitutive IL-2 expression in MLA 144, we have isolated and characterized cosmid clones representing a normal and a doubly inserted IL-2 allele in this cell line. The map of the normal MLA 144 IL-2 allele closely resembles that of the normal human IL-2 gene. The abnormal allele contains a 3' insertion that is a GaLVSF provirus with two long terminal repeats (LTR) and an internal 3.25 kb deletion. At the 5' end of the abnormal allele is a second insertion that DNA sequencing showed to be an isolated GaLVSF LTR with a transcriptional orientation opposing that of the IL-2 gene. We demonstrate by Northern blotting analysis that the vast majority of transcripts are from the abnormal allele, implying that one or both retroviral insertions are responsible for constitutive expression of the allele.

The Daudi cell line, established from a Burkitt lymphoma, has recently been found to be HLA- andΒ2-microglobulin-negative, although it expresses B lymphocyte alloantigens. This report is concerned with the reexpression of HLA-A10, B38, and B17 on the Daudi cell, after cell fusion with another human cell line (Raji) or with mouse fibroblasts. In the latter fusion, the same HLA specificities are re-expressed, but not humanΒ2-microglobulin while mouseΒ2-microglobulin andH-2 could be detected. No such reexpression was observed when Daudi was fused with the F9 mouse teratocarcinoma, which lacks mouseΒ2-m andH-2. No HLA activity (alloantigenic and xenogenic activity) was detected in the membrane or cytoplasm of Daudi, using salt extraction and sonication. Therefore we postulate thatΒ2-microglobulin could be necessary for the expression and possible synthesis of the HLA antigen.

The hybridoma technique was used to produce a monoclonal antibody specific for a polymorphic determinant on human Ia antigens. BALB/c mice were immunized with a B-lymphoblastoid cell line derived from an HLA-DR3/DR4 positive donor. Hybridoma culture supernates were screened in two stages by means of the microcytotoxicity assay. Supernates were first tested against the Ia-positive immunizing cell line and against Ia-negative cells. Cultures identified as producing antibody cytotoxic for the immunizing cell line but not for Ia-negative cells were subcultured and the supernates then tested against a selected panel of HLA-D homozygous cell lines (HCL). In this manner, it was possible to identify a microwell of hybrid cells producing an antibody that reacted with a polymorphic HLA-DR determinant. Cells from this culture, designated 17.15, were cloned twice by limiting dilution. Specificity was evaluated with a panel of 39 HCL and B cells from 70 normal donors. Antibody 17.15 recognized a supertypic DR“4+5” specificity, which was also present on DRw9 and some DR7 positive cells. These findings suggest that the cross-reactivity groups DR“4+5” (MB-3) and DR“4+7” (MT-3) defined by alloantisera may share a common supertypic specificity that is recognized by monoclonal antibody 17.15.

Six mouse and 13 rat monoclonal antibodies (mAb) recognizing HLA-DR, DQ and DP antigens were used for the detection of cell surface class II MHC antigens of equine lymphocytes. The monoclonal antibodies were tested against peripheral blood lymphocytes (PBL) from a panel of thoroughbred horses, using two-color fluorescence flow cytometry. Seven of these mAbs reacted with both surface immunoglobulin positive (sIg+) and surface immunoglobulin negative (sIg-) lymphocytes. sIg+ cells stained consistently brighter than sIg- cells. The fluorescence pattern did not vary from donor to donor for each of the mAbs tested, except for SFR1-MI.2, which reacted with a variable intensity with cells from 47 of 53 horses tested. Immunoprecipitation with mAb SFR1-MI.2 and analysis by two-dimensional electrophoresis demonstrated the presence of light and heavy chains equivalent to HLA class II alpha and beta chains. Antibody N297 (DQ specific), previously shown to react with an epitope expressed on human B cells but not on mitogen-induced T cells, reacted only with sIg+ cells in 42 of 53 horses tested. The lack of staining of horses sIg- cells with N297 may be due to a low or lack of expression of this determinant on these cells or to a weak cross-reactivity of this antibody with equine antigens.

Two-dimensional gel electrophoresis was used to compare immunoprecipitated, radiolabeled HLA-DR molecules synthesized by alveolar macrophages (AM) and blood monocytes (BM) of the same healthy, nonsmoking volunteers. No charge differences were noted by isoelectric focusing. Molecular weight analysis of HLA-DR from AM revealed a complex pattern of radioactive spots differing slightly in molecular weight. This pattern was apparent in both the alpha and the beta chains. In contrast, a simpler pattern without the slight molecular weight differences was noted in HLA-DR from BM. The differences were eliminated by labeling AM and BM in the presence of tunicamycin, a specific inhibitor of protein-carbohydrate linkages of the N-glycosidic type. Thus, it appears that neutral, N-linked carbohydrate moieties account for the differences in HLA-DR molecules between AM and BM. The differential glycosylation of HLA-DR molecules in AM and BM may relate to mononuclear phagocyte development as well as antigen-presenting func...

The immunosuppressive agent, cyclosporine, has been found to augment receptor-stimulated calcium fluxes in isolated hepatocytes. After treatment of Quin 2-loaded hepatocytes with cyclosporine, both the amplitude and duration of the vasopressin-induced rise in the cytosolic free Ca2+ are increased. These effects are dependent upon the concentration and time of exposure of the cells to cyclosporine. Cyclosporine increases both 45Ca2+ influx across the plasma membrane and the cellular calcium content. The total cellular magnesium, sodium, and potassium contents are not affected by cyclosporine. However, cyclosporine treatment, per se, has no apparent effect on the cytosolic free Ca2+ concentration as assayed by Quin 2 fluorescence. The increase in total cell calcium is associated with progressive increases in the calcium content of the endoplasmic reticular and mitochondrial calcium pools. The vasopressin-induced net efflux of Ca2+ from hepatocytes was 2-fold greater after treatment with 10 micrograms/ml cyclosporine for 10 min, but the lag time prior to the onset of Ca2+ efflux was not affected. These results are interpreted on the basis of cyclosporine having a primary effect on increasing the permeability of the plasma membrane to Ca2+, thereby leading to an increase of the calcium content of the hormone-sensitive intracellular calcium pool.

DQw3 polymorphism has been described previously at the serologic, biochemical, and genomic level (1–8). In the present study, HLA class II α and β chain polymorphism was investigated by two-dimensional (2-D) gel electrophoresis of immunoprecipitated molecules in a panel of 27 HLA-DQw3 lymphoblastoid cell lines (Table 1).

The polymorphism of HLA antigens detected by various methods (i.e., conventional serology, monoclonal antibodies, T-cell clones, electrophoresis, or restriction fragment analysis) reflects differences among cells at the DNA level, at the protein level, or at the assembly/posttranslational level. Correlation of the polymorphisms identified by these individual procedures provides insight into the structural/functional relationship of these antigens.

Thymic processed lymphocytes subpopulations were assayed in 32 healthy patients with hemophilia A and no inhibitor. Commercial concentrates were infused at various frequencies. Monoclonal antibodies to OKT3, OKT4 and OKT8 were measured and compared to age controls. A progressive decrease in percent OKT4 cells, a progressive increase in percent OKT8 cells and gradual decline in the T4/T8 ratio were noted with increase in the patients' age. A correlation between the amount of concentrate received and alteration in T cell subsets was observed in 4 children only. These early and progressive alterations in the T-lymphocyte subsets suggest early immunocompromise and warrant close patient surveillance and immunologic scrutiny.

The chromatin structure of the interleukin-2 (IL-2) gene was probed by DNase I treatment of isolated nuclei. The 5' region of the IL-2 gene contains three regions of hypersensitivity to DNase I. When peripheral blood T cells or Jurkat T cells are stimulated with mitogens, IL-2 message is induced, and the promoter region of the IL-2 gene develops an additional hypersensitive site. This suggests that a DNA sequence close to the transcriptional start site is involved in the transduction of the extracellular signal. Such a conclusion is further supported by DNA transfection experiments. A short segment of DNA, which includes the region of induced hypersensitivity, confers inducibility on the linked chloramphenicol acetyltransferase gene in transiently transfected Jurkat cells. In addition, cells of nonhematopoietic origins exhibit a strikingly different chromatin pattern of IL-2, suggesting a role during differentiation for some of the hypersensitive sites.

Fifteen DR4-bearing haplotypes from twelve patients with insulin-dependent diabetes mellitus (IDDM) were analyzed serologically, cellularly, and biochemically. The HLA-Dw composition of these DR4-positive haplotypes was Dw4 (46%), Dw14 (22%), and Dw10 (33%). The biochemical analysis by two-dimensional electrophoresis (2D-PAGE) of the DR beta chains showed that each Dw specificity is characterized by a specific DR4 beta chain that appears to be identical in normal and diabetic individuals. Analysis of DQ beta chains in the DR4-bearing haplotypes revealed that certain Dw specificities such as Dw4 are characterized by the presence of either the DQw7 (formerly DQw3.1) or DQw8 (formerly DQw3.2) alleles, which generate the Dw4.1 or Dw4.2 subtypes, respectively. Others such as Dw14 and Dw10 are characterized by the presence of the DQw8 allele. In our sample of 12 patients the Dw4.2 (Dw4, DR4 beta I-4 DQw8) and Dw10 (Dw10, DR4 beta I-1, DQw8) subtypes were predominant. It is concluded that individual DR beta and DQ beta gene products from the DR4-bearing haplotype of IDDM patients are identical to those of normal control subjects and that Dw14 as well as Dw10 are involved in disease susceptibility. We suggest that disease susceptibility may be influenced by more than one locus within the HLA-D region.

CLINICOPATHOLOGICAL studies suggest that the T-cell lymphomas are heterogeneous with respect to clinical presentation, course, and morphology. Mycosis fungoides and the Sezary syndrome affect the s...

Two distinct differentiation antigens of human myelomonocytic cells are defined using murine monoclonal antibodies. The antigens recognized by antibodies 20.2 and 20.3 are expressed by all cells of the monocyte lineage in both peripheral blood and bone marrow. Cell-sorting experiments demonstrated that histiocytes and immature bone marrow cells with detectable α-naphthyl butyrate esterase activity also express both antigens. Within cells of other lineages, the antigens had distinct patterns of expression. Immature myeloid cells were 20.2 negative, but 20.3 positive; whereas mature myeloid cells were 20.2 positive, but 20.3 negative. Nucleated erythroid cells and platelets expressed only the 20.3 antigen. These results indicate that myeloid and monocytic cells share common differentiation antigens with cells of the erythroid and megakaryocytic lineages. The 20.2 and 20.3 antibodies reacted with the leukemic cells from some patients with acute nonlymphocytic leukemia (FAB, M1-M5) and with some cell lines derived from patients with nonlymphocytic leukemia, but not with blast cells from patients with lymphoid leukemia or with lymphoid leukemic cell lines. These antibodies may prove useful in studying the differentiation of bone marrow stem cells, in defining the cellular origins and classification of leukemias, and in the identification of distinct prognostic subgroups of acute nonlymphocytic leukemia.