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Biomedical subjects

P Kuśnierczyk

Publications and source records attributed to P Kuśnierczyk.

At least 19 recordsLinked to original sources
PubMed2006

Inhibitory and activatory KIR gene frequencies in the Polish population.

Killer cell immunoglobulin-like receptors (KIRs) present on natural killer cells and minor subpopulations of T cells recognize class I human leukocyte antigen (HLA) molecules on the surface of target cells. Human individuals differ by the presence or absence of some KIR genes on their chromosomes (haplotypic polymorphism). As KIRs (especially two-immunoglobulin-domain-like containing, or KIR2D, molecules) are important for the outcome of tissue (particularly for haematopoietic stem cell) transplantation and possibly for pregnancy, the knowledge of KIR gene distribution in a given human population is of practical value. Therefore, we tested 175 healthy individuals from Poland for the presence or absence of these KIR genes which show haplotypic polymorphism and are expressed. Results were compared with those published for other human populations, showing close relations with other Caucasoids.

Chromosomes, Human↗
PubMed2006

CTLA-4 gene polymorphisms and natural soluble CTLA-4 protein in psoriasis vulgaris.

CTLA-4 molecule is an important inhibitor of T-lymphocyte activation. Several single nucleotide polymorphisms (SNPs) in the CTLA-4 gene were found, and their associations with many human diseases were described. So far, however, such studies have not been performed in psoriasis vulgaris in Caucasoids. Therefore, we examined the distribution of three CTLA-4 SNPs: -1147C/T, -318C/T and +49 A/G in 116 patients with psoriasis vulgaris and 123 healthy blood donors using the polymerase chain reaction-restriction fragment length polymorphism method. For all three SNPs, the frequencies of alleles, genotypes and three-point haplotypes were very similar in patients and controls, suggesting no contribution of these genetic variants to psoriasis.

Adult↗
PubMed2004

A novel polymorphism in the cytoplasmic region of the human immunoglobulin A Fc receptor gene.

The Fc receptor for immunoglobulin A (IgA), FcalphaRI, is expressed on several types of myeloid cells, and activates them upon ligand binding. However, binding of IgA to the extracellular domain of the receptor requires previous stimulation of the cell by cytokines, and the cytoplasmic tail of FcalphaRI has been shown to play a role in this. Therefore, polymorphism in this region might affect this process. However, no changes in the amino acid sequence in this region of the FcalphaRI have so far been reported. Here, we describe for the first time a single nucleotide polymorphism in exon 5 of the immunoglobulin A Fc receptor (FCAR) gene leading to a Ser-->Gly substitution at position 248 of the mature FcalphaRI protein. Prediction of structural features suggests some changes that may affect the function of the protein to some extent. However, the Gly248 variant is quite common (4% homozygotes and 38% heterozygotes) in healthy population, suggesting a weak effect, if any, on function, at least in heterozygotes.

Amino Acid Sequence↗
PubMed2001

Hematological effects of intermittent 2-hour infusions of cladribine in multiple sclerosis patients: a comparison of 2 dosage patterns.

Cladribine is a lymphocytotoxic purine nucleoside with potential for treatment of autoimmune diseases. However, optimal administration regimens remain to be established. Twenty multiple sclerosis patients enrolled into this study were given 30 intermittent 2-hour cladribine infusions (0.07 mg/kg per infusion) each. Ten patients received cycles of 5 consecutive daily infusions at 5-week intervals (clustered dosage) on an inpatient basis; the other 10 patients received 1 infusion weekly (nonclustered dosage) on an outpatient basis. Red blood cell (RBC), platelet, and total white blood cell (WBC) counts were assessed at 5-week intervals during the treatment and at 13-week intervals during a 26-week follow-up period. Major WBC and lymphocyte subsets were assessed cytometrically at 15-week intervals during the treatment and at 13-week intervals thereafter. The clustered dosage produced a lasting decline in granulocyte count, a delayed decrease in monocyte count, and a transient decrease in RBC count. The nonclustered dosage caused a larger and persistent decline in RBC count, a smaller (P = .051. compared over the study period) decrease in monocyte count, and no change in granulocyte count. Both regimens transiently reduced natural killer and B-cell subsets (by 40%-60% and >80%, respectively) and caused lasting declines in CD4+ T-cell subsets (by >50%). No significant change was found in CD8+ T-cell subsets. These results show similar potency of these regimens with respect to major lymphocyte subsets, while suggesting that the nonclustered dosage is less toxic to myeloid precursors and more toxic to erythroid lineage precursors.

Adult↗
PubMed2001

Effect of IFN-gamma on expression of HLA in bare-lymphocyte syndrome-like cell line HAJ.

We compared HLA antigen expression on new B-lymphoblastoid cell line (B-LCL) HAJ with that on B-LCLs expressing normal HLA levels as well as on B-LCLs derived from bare lymphocyte syndrome (BLS) patients and in vitro mutated B-LCLs of BLS-like phenotype. HAJ cells had no expression of HLA class II and low expression of class I antigens similarly to some of BLS B-LCLs, although HAJ cell line was derived from lymphocytes of HLA class I- and class II-normally expressing donor. HAJ cells displayed B lymphocyte markers, surface immunoglobulin and CD19. Culture of HAJ cells in the presence of interferon y resulted in HLA class I antigen upregulation, but did not restore class II expression. The cell line HAJ may prove useful for studies on factors influencing HLA class I cell surface expression.

Animals↗
PubMed2000

Octapeptide but not nonapeptide from HIV-1 p24gag protein upregulates cell surface HLA-C expression.

OBJECTIVES: The HLA-Cw3 molecule has been reported to present peptides derived from HIV-1 p24gag protein to a cytotoxic T lymphocyte clone. We have shown previously that the synthetic octapeptide 145-152 derived from the p24gag sequence upregulated cell surface HLA-C expression on HLA-Cw*0303+ cells. Here, we examined the question of whether the nonapeptide 144-152 also exerts a similar effect. METHODS: The HLA-Cw*0303+ B-LCL PAJ and control HLA-Cw3-negative cells B-LCL HAJ and T-LCL 500/C9 were used. HLA expression on peptide-pulsed and non-pulsed cells was evaluated using specific antibodies and flow cytofluorimetry. Binding of dansylated peptides onto different cell lines was measured spectrofluorimetrically. RESULTS: The HIV-1 p24gag octapeptide upregulated cell surface HLA-C on PAJ (Cw*0303+) cells, whereas the nonapeptide did not. HLA-A2 expression was not affected by these peptides. Specificity of the effect of octapeptide was confirmed by the lack of HLA-C upregulation on HLA-Cw3- cells and by lower binding of dansylated peptide to the HLA-Cw3- cells HAJ and 500/C9. CONCLUSIONS: The above results indicate that HLA-Cw*0303 preferentially binds the octapeptide rather than the nonapeptide derived from HIV-1 p24gag protein.

Antibodies, Monoclonal↗
PubMed1999

[Antigen peptide/MHC complex as an initiator of a signal for lymphocyte T activation].

T lymphocytes recognize antigens in the form of oligopeptides bound by major histocompatibility complex (MHC) molecules. This recognition is specific due to clonally distributed receptors (T cell receptors, TCRs) that are specific for a given peptide/given MHC combination. Recognition of appropriate (agonist) peptide bound to appropriate (usually self) MHC molecule results in conformational change in the TCR that is transmitted to TCR-associated CD3 gamma, delta, epsilon and zeta polypeptide chains. These chains then undergo a series of tyrosine phosphorylations which, in turn, cause transmission of the activation signal further along the intracellular signaling pathway. However, there are peptides (partial agonists or antagonists) that induce only incomplete signal transmission, leading to the expression of only some, but not the other, T cell functions, to the anergy, or to the apoptosis. All these situations might be exploited in future for specific immunotherapy of different pathologic conditions. Advantages and disadvantages of this approach are briefly discussed.

Immunotherapy↗
PubMed1998

Human in vitro cell lines verification by minisatellite DNA restriction fragment length polymorphism.

Four families of human in vitro cell lines were tested for minisatellite restriction fragment length polymorphism (RFLP) using multilocus probes MZ1.3 and/or 33.15 after digestion of DNA with restriction enzymes HinfI or HaeIII. These results confirmed that (i) the RFLP pattern is relatively stable in established cell lines and, therefore, could be used as a specific marker of a cell line identity, (ii) the use of MZ1.3 and 33.15 probes permits the identification of hybridomas and (iii) one of the cell lines tested, a lymphoblastoid cell line HAJ, may possess a hot spot of mutation.

Cell Line↗
PubMed1998

Studies on binding of HIV-1 p24gag peptide to HLA-Cw3+ cells.

Human major histocompatibility complex class I antigens, HLA-C, are expressed on the cell surface at approximately a tenfold lower level than HLA-A and -B. We hypothesized that the expression of HLA-C is limited by the quantity of high affinity peptides which bind to these molecules, thus allowing only a small fraction of HLA-C molecules to be transported and/or to remain stable on the cell surface. If this assumption is correct, then the addition of exogenous peptide should increase cell surface HLA-C expression. To verify the hypothesis, we pulsed lymphoblastoid cell line PAJ (HLA-Cw3+) with synthetic HIV-1 p24gag 145-152 peptide, known to be presented to T-lymphocytes by HLA-Cw3 molecule. PAJ (HLA-Cw3+) cells bound approximately two times more of the peptide than HAJ (HLA-Cw3-), and four times more than 500/C9 (HLA-Cw3-) cells. Accordingly, overnight pulsing of PAJ cells with the p24gag 145-152 peptide caused an increase in class I HLA expression detected on the cell surface by flow cytofluorimetric analysis with anti-HLA-B,C monoclonal antibodies but not by anti-HLA-A antibody. In contrast, HLA-Cw3- cells treated in the same manner did not show any increase of HLA class I expression. Our data suggest that low concentration of high affinity peptides within the cell may be one of the factors limiting cell surface expression of HLA-C molecules.

Antibodies, Monoclonal↗
PubMed1996

[Allelic and haplotypic polymorphism of HLA-DR].

In this short review, genomic organization of HLA-DR region is presented. Five main DR haplotypes are depicted in schematic figures listing alleles of active DRB genes in each haplotype group. Numbers of different DR molecules which can be produced in individuals possessing various haplotype combinations are shown.

Alleles↗
PubMed1996

A new lymphoblastoid cell line defective in class II HLA expression.

A lymphoblastoid cell line, HAJ, was derived by in vitro transformation with Epstein-Barr virus of peripheral blood lymphocytes (PBL) from a patient with renal insufficiency awaiting kidney graft. Cell surface expression of class I and class II HLA molecules was determined by flow cytofluorimetry using monoclonal antibodies and compared with that of cell line PAJ similarly derived from a healthy donor. HAJ cells expressed class I antigens at levels comparable with PAJ cells. In contrast, class II antigens were absent from the cell surface of HAJ cells while they were abundant on PAJ cells. Permeabilization and fixation of cells with acetone/formaldehyde solution revealed intracellular Ki-67 antigen but not class II HLA molecules. The genes for HLA-DR beta, DQ alpha and DP alpha were present in the HAJ genome as detected with polymerase chain reaction (PCR) using locus-specific primers amplifying a second exon. In RT (reverse transcriptase)-PCR, transcripts of DQA1 and DPA1 genes were easily detectable in PAJ (positive control) but not in HAJ cells. These results suggest a defect in HAJ cells of transcription of genes for all class II antigens. The cell line HAJ may prove to be an interesting model for in vitro studies of molecular mechanisms of the regulation of class II expression.

Biological Transport↗
PubMed1995

[Biological role of HLA-C].

Human major histocompatibility complex class I molecules, HLA-A and -B, bind peptides derived from intracellular proteins, transport them to the cell surface and present them to T lymphocytes. Much less is known about the function of the third "classical" class I molecule, HLA-C. Recent data disclosing remarkable polymorphism of HLA-C, possible importance of this molecule for the recognition of target cells by nature killer cells, and capability to present viral antigens to the T lymphocytes are reviewed. Preliminary results from our laboratory on binding of synthesis peptides to HLA-Cw3+ cells are presented.

Animals↗
PubMed1994

Absorption with K562 erythroblastoma cells as a means for discrimination between auto- and alloantibodies in sera of hypersensitized renal patients.

We applied K562 erythroblastoma cell line as a substitute for autologous lymphocytes in the absorption of autoantibodies from sera of 26 hypersensitized renal patients exhibiting high degree of cytotoxic reactivity with a panel of lymphocytes from unrelated individuals (panel reactivity, PRA). All of analysed sera contained allo-reactivity before absorption. After removal of autoantibodies, 85% of the sera still contained alloantibodies whereas in 15% of the sera no alloreactivity was detectable. Absorption of high PRA sera with K562 cells and with autologous lymphoblastoid cell lines derived by transformation with Epstein-Barr virus (EBV-LCL) gave substantially the same results. As autoantibodies have reportedly no effect on kidney graft survival, the autoabsorption of high PRA sera may increase the chance of patients in whom only autoantibodies were detected to receive the transplant. Application of K562 cells, instead of autologous lymphocytes/lymphoblasts, is recommended whenever high numbers of patient's cells are not available. It may be particularly suitable for routine clinical laboratories, not equipped and prepared for derivation and propagation of EBV-LCL.

Adult↗
PubMed1994

Determination of immunoglobulin class of alloantibodies in sera from hypersensitized renal patients.

26 sera from hypersensitized renal patients were analysed for immunoglobulin class of alloantibodies. To assess the participation of IgM and IgG in alloreactivity, sera were treated with dithiothreitol (DTT) or Staphylococcus aureus protein A (SpA), respectively. Treatment with both DTT and SpA was also performed to test the possible contribution of other immunoglobulin classes. Immunological complexes which may mimic alloreactivity were excluded by polyethylene glycol (PEG) treatment. Immunochemically modified sera were tested against a panel of allogeneic B and T lymphocytes. IgG class alloantibodies reactive with B lymphocytes were found two times more frequently than those reactive with T lymphocytes. In 22% of sera only IgM alloantibodies were detected. No contribution of other immunoglobulin classes of immune complexes was seen. Our results show that DTT and SpA treatment are technically simple and reproducible methods of discriminating between IgG and IgM alloantibodies and can be recommended for routine use in clinical analysis of sera from hypersensitized renal patients awaiting kidney graft.

Adult↗
PubMed1987

Genetic monitoring of inbred mouse strains maintained at the Bhabha Atomic Research Centre, Bombay: serological typing for H-2 haplotypes and lymphocyte differentiation markers.

Seven inbred mouse strains, AKR, CBA, C3H, C57BL/6, C57BR/cd, DBA/2 and Swiss, maintained at the Bhabha Atomic Research Centre, Bombay (designated Bh) were monitored for compatibility with standard strains as well as for genetical homogeneity. For this purpose, five individual mice from each strain were typed serologically for H-2 class I and class II antigens and for lymphocyte differentiation markers, Thy-2, Lyt-1, Lyt-2, TL and Ly-10. In this latter testing, 15 inbred strains from the Institute of Immunology and Experimental Therapy, Wrocław (designated Iiw) were included. Results revealed that none of the tested strains deviated from the reactivity pattern of standard strains described in the literature. No evidence of genetic contamination was found in any strain. In the course of these studies, several interesting observations were made: (1) Swiss/Bh strain is an intra H-2 recombinant, probably KdAbEbDbTlab, (2) C3H/Bh and C3H/Iiw are Ly-10a and Ly-10b, respectively (3) some (CBA, C3H, DBA/2 and GR/S) but not C58/Ly-2a strains cross reacted with high concentration of anti Lyt-2.2 monoclonal antibody HO.2.2.

Animals↗
PubMed1987

Crossreactivity of anti Lyt-2.2 monoclonal antibody with some Lyt-2.2-negative mouse strains.

We observed that thymocytes from some Ly-2a (i.e., Lyt-2.2-) mouse strains crossreacted with high concentrations of anti Lyt-2.2 monoclonal antibody HO.2.2, whereas other Ly-2a strains were clearly negative. Inbred strains from two breeding colonies (Wrocław and Bombay) exhibited the same pattern of reactivity with HO.2.2. The nature of crossreacting antigen is discussed.

Animals↗