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Biomedical subjects

H Festenstein

Publications and source records attributed to H Festenstein.

At least 91 records · Page 5Linked to original sources

Control of synthesis and expression of H-2 heavy chain and beta-2 microglobulin in AKR leukemias.

In a series of newly isolated AKR leukemias, some tumors expressed large amounts of both H-2K and H-2D molecules, while others had reduced levels of both antigens. The number of H-2 antigens expressed in steady state showed a consistent correlation with the rate of synthesis of the H-2 class I heavy chain and the beta-2 microglobulin (beta 2m) light chain, and with the amount of H-2- and beta 2m-specific mRNA present in the tumors. Stimulation of leukemic cells with interferon induced an increased transcription of both H-2 and beta 2m mRNA. These results suggest that there is a mechanism that regulates, at the transcriptional level, the coordinate expression of H-2K and H-2D heavy chains, and the beta 2m light chains encoded by genes on chromosomes 17 and 2, respectively.

Animals↗

Identification of murine H-2Db histocompatibility antigens in cells transfected with cloned H-2 genes.

Clones of mouse L-cells transformed with 21 cosmids containing 15 major histocompatibility complex class I genes of C57BL10 (H-2b) sperm cell DNA were analyzed for the expression of their transfected H-2 and Qa/Tla genes. Three cosmids contained a single gene, mapping to the H-2D region. This gene encodes the H-2Db alloantigen: mouse L-cells transfected with cosmids containing this gene reacted with monoclonal antibodies and alloantisera specific for the H-2Db antigen and expressed a 46-kd H-2 heavy chain associated with beta 2-microglobulin in their cell membranes. Furthermore, these transfected cells were stimulators of, and targets for, anti-H-2Db cytotoxic T-lymphocytes. Eighteen cosmids contained 14 different genes mapping to the Qa and Tla regions. L-cells transfected with these genes did not express class I genes reacting with alloantisera or monoclonal antibodies against Qa2, Qa4 or TL differentiation antigens. In particular, the Qa2,3 gene of C57BL10 was not identified.

Animals↗

A new HLA Bw16 subtype defined in both Negroid and Saudi Arabian populations.

Serological identification of a new HLA-Bw16 subtype, B39B, was made by the analysis of reaction patterns of many alloantisera and one monoclonal antibody. The B39B pattern of reactivity was shown to be distinct from HLA-Bw38, Bw39, and 8w57. Cytotoxicity testing before and after absorption suggests that the B39B specificity belongs to the HLA-B7 cross-reactive group. The B39B was clearly demonstrated in two families. This antigen was detected in Negroids and Saudi Arabian Caucasoids but not in a large panel of British Caucasoids.

Black People↗

Two different T-cell systems in humans, one of which is probably equivalent to Qa or Tla in mice.

Two different alloantigenic systems, expressed mainly on TG and TM lymphocytes and called TCA and TCB, respectively, are described. Alloantisera from parous women are absorbed with Epstein-Barr virus-transformed B cell lines from the husband of the serum producer to remove all anti HLA-A,B,C and DR antibodies. The absorbed sera are tested against a random panel and against lymphocytes from families. Family studies indicate that the TCA system might be encoded by a gene linked to HLA and located on the telomeric side of HLA-A. The total lod scores for the material of 15 informative families is +3.301 at a recombination fraction of 15%. Furthermore we can show that the TCA molecule is associated with beta 2-microglobulin by blocking with turkey anti-beta 2 microglobulin. The antigens are dimers of peptides with a molecular weight of approximately equal to 42,000 daltons and 12,000 daltons, respectively. This implies that TCA might be equivalent to either Qa or Tla in the mouse. For the TCB system no evidence is found for linkage with any known genetic marker. Only in random population studies is an association seen between TCB and Gm.

Animals↗

HLA polymorphisms in Saudi Arabs.

The HLA-A, -B, -C, -DR, Bf and GLO phenotypes of 109 unrelated Saudi Arab males have been determined. HLA-A and -B antigen frequencies were compared with data reported for European Caucasoids and various Arab populations. Most similarities in antigen frequencies were seen between Saudi Arab and Iraqi populations. A high frequency of Bw50 was observed in Saudi Arabs. The frequencies of HLA-DR antigens in Saudi Arabs were compared to European Caucasoids. HLA-DR7 was at high frequency in Saudi Arabs. Linkage disequilibria between alleles of HLA loci was examined. Many instances of previously reported antigen associations were seen in Saudi Arabs, together with a number of associations which have not been described elsewhere. HLA-Cw6-Bw50-DR7-BfS0.7 is suggested as being a common haplotype in Saudi Arabs.

Complement Factor B↗

Immunochemical analysis of class II molecules expressed by a human B cell line with the unusual class II genotype, DR5+, MB1+, (MB3-), MT2+.

The human B lymphoblastoid cell line FPA was established from a consanguineous individual homozygous for the unusual serologically defined Class II genotype, DR5+, MB1+, (MB3-), MT2+. The MB1 allodeterminant is classically found only in association with DR1, 2, or w6 and DR5 is almost invariably associated with MB3. Class II molecules expressed by this unusual DR5 homozygous cell line have been characterized by immunochemical analysis using two-dimensional gel electrophoresis. These molecules were isolated from the FPA cell line by anti-DR5, anti-MT2, and anti-MB1 allosera, as well as a monoclonal antibody which defines an MB1-like determinant. However, an anti-MB3 alloserum and a monoclonal antibody which defines an MB3-like determinant did not immunoprecipitate Class II molecules from FPA. These studies document that the MB1 allodeterminant resides on DS molecules from this DR5 cell line and provide additional evidence that MB1 and MB3 are alleles of the same Class II antigen system.

B-Lymphocytes↗

Different functions and associations of HLA-DR and HLA-DQ(DC) antigens shown by serological, cellular and DNA assays.

Two consanguineous Caucasoid HTCs, DHI and FPA, were investigated, the latter having an unusual HLA-DR/DQ(DC) association. Both these HTCs typed clearly as HLA-DRw11. However, while DHI typed as DRw11/DQw3(DC4) as expected, FPA typed as DRw11/DQw1(DC1) instead. Although extremely rare in Caucasoids, DRw11/DQw1 is a common pattern of association in Nigerian Negroids. Southern blots of DNA extracted from EBV cell line derived from FPA, hybridized with HLA-DC alpha and HLA-DC beta probes, confirmed this unusual DRw11/DQw1(DC1) association. In addition the DC alpha probe showed a unique additional restriction fragment length polymorphism (8 kb) attributable to the DX gene in the FPA DNA. When DHI and FPA were used as stimulators in MLC, the patterns to typing responses obtained were not completely concordant although they overlap to some extent. For this reason FPA has been locally designated Dw'F5', distinct from Dw5. Furthermore, the HLA-DQ antigens of the responder cells were not necessarily the same as those of the HTCS to which they gave typing responses (FPA and DHI). Functional studies using these two HTCs showed that the DQ(DC) antigens probably have no direct lymphocyte activating properties but rather have a regulatory role in controlling responses to allodeterminants in MLC.

Antibodies, Monoclonal↗

HLA polymorphisms in Nigerians.

The HLA class I and class II phenotypes of a panel of 114 unrelated Nigerians have been determined. The panel was tested for all the known class I antigens and comparisons of the HLA-A and -B frequencies with those of other African Negroid populations revealed some differences. Only limited comparisons could be made for the HLA-DR and -D frequencies as these are not available for any well-defined African Negroid population. The data concerning the class II antigens of this panel are the most interesting. Half of the DRw11-positive panel members are DQw3 negative and DQw1 positive. In addition, there is dissociation of some HLA-D and -DR specificities, a number of panel members are positive for an HLA-D specificity and are negative for the corresponding HLA-DR specificity. Our results show the value of population studies in the investigation of the relationship between the different HLA class II antigens.

Black People↗

Differential expression of HLA-DR and HLA-DQ antigens on normal cells of the myelomonocytic lineage.

We have previously shown that HLA-class II antigens have a differential expression on acute myeloblastic leukaemia (AML) blasts. These cells express HLA-DR molecules but the HLA-DQ antigens are undetectable. In this paper we study the expression of HLA-DR and HLA-DQ antigens, using monoclonal antibodies (MoAbs), on normal cells of the myelomonocytic lineage: the common myelomonocytic progenitor (CFU-GM) and the monocytes, by techniques of inhibition of CFU-GM growth and double immunofluoroscence, respectively. The results show that HLA-DR and HLA-DQ antigens are differentially expressed on normal myelomonocytic cells. While HLA-DR molecules are expressed on CFU-GM and on the majority of peripheral blood monocytes, HLA-DQ antigens are not expressed on CFU-GM and only present on a subpopulation of monocytes. This data further confirms that HLA-DR and HLA-DQ molecules are coded by different genes with independent regulation of the gene expression not only on myeloid leukaemias but also on normal cells of the myelomonocytic lineage.

Adult↗

Association of HLA-DR4/Dw4 and DR2/Dw2 with radiologic changes in a prospective study of patients with rheumatoid arthritis. Preferential relationship with HLA-Dw rather than HLA-DR specificities.

Patients admitted to a prospective study within a year of onset of suspected rheumatoid arthritis showed a positive correlation between HLA-Dw4 and the eventual severity of peripheral radiologic changes. Dw4 and DR4 were strongly associated with severity of erosions when analysis was restricted to each of the following: patients with erosions, those under 50 at onset, and all females. Relationships were consistently stronger with Dw4 than with DR4. Another D-related specificity, MT3, was positively correlated and Dw2/DR2 negatively correlated with erosions.

Age Factors↗

Soluble Mlsa antigens: stimulatory effect in vitro versus suppressive effect in vivo.

Using a pair of congenic strains of mice differing only at the Mls haplotype (Mls locus and closely linked genes), BALB/c (Mlsb) and BALB.D2-Mlsa, we have compared the in vitro proliferative responses of Mlsb lymphocytes to Mlsa antigens presented on either lymph node cells (LNC) or peritoneal adherent cells (PAC). Results showed that Mlsa-PAC are stronger stimulators than Mlsa-LNC, and furthermore, that the supernatant from Mlsa-PAC may be effective in eliciting a lymphocyte proliferative response. The proliferation in response to PAC supernatant is partially due to activation by nonspecific factor(s); however, the response in the presence of Mlsa incompatible PAC supernatant is about three times greater than the response obtained in the presence of syngeneic Mlsb-PAC supernatant, suggesting an additional stimulation by soluble Mlsa antigens. Contrasting with the ability of PAC-supernatant to stimulate a primary proliferative response in vitro, the in vivo immunization of Mlsb mice with Mlsa-PAC supernatant abrogates the specific proliferative response in subsequent one-way mixed lymphocyte cultures. This abrogation of the specific response is comparable to that observed after immunization with intact Mlsa peritoneal or spleen cells, although in the latter case the anti-H-2 proliferative response is also decreased, regardless of whether the H-2 incompatible stimulating cells express an additional incompatibility for Mlsa. The proliferation of untreated, but not of Mlsa-immunized BALB/c LNC, is stronger in cultures with DBA/2 stimulating cells (incompatible for Mlsa and other non-H-2 antigens) than in cultures with BALB.D2-Mlsa cells (incompatible for Mlsa alone), and is comparable in intensity to that activated by H-2 incompatibility. We conclude that Mlsa antigens are more efficiently recognized by unprimed helper T cells when presented on PAC than when presented on LNC. In the primary proliferative response, the effects of Mlsa and other non-H-2 antigens may be cumulative. In vivo immunization against Mlsa antigens results in suppression of the specific proliferative response and, to a certain extent, of the nonspecific proliferative response (directed against both H-2 and other non-H-2 antigens). Since Mlsa antigens are obtainable in soluble form, their physico-chemical purification can now be envisaged.

Animals↗

HLA polymorphisms in a Shanghai Chinese population.

The frequencies of the HLA-A, B, C, D, DR and MB antigens have been determined in a homogeneous Shanghai Chinese population. Comparisons with the HLA-A and -B frequencies in other subsets of the Chinese population revealed some marked differences. No comparisons were possible for the D, DR and MB antigens since there were no previous studies of the antigens in those loci. We suggest that studies of the Chinese population should be confined to clearly defined homogeneous subsets. In this manner, the confounding effect of population heterogeneity may be avoided, and it is this heterogeneity which calls for extensive surveys of the huge Chinese population.

Asian People↗

HLA antigen associations with extra-articular rheumatoid arthritis.

Seventy-seven patients with rheumatoid arthritis were investigated to examine the frequency of HLA antigens and their relationship to clinical and serological manifestations of extra-articular disease. The phenotype frequencies of DR4, DRw53, Bw62 and Cw3 were significantly increased, compared to normal controls, and there were negative associations with DR2 and DR7. The HLA antigen in strongest association with rheumatoid arthritis was DR4 (73.6%) and the relationship with DRw53 appeared to be secondary. The frequency of DR4 rose to 92% in seropositive patients with extra-articular disease manifestations whose serum contained immune complexes. A high frequency of DR4 was also seen in male patients (86%), reaching 100% in the small group of seropositive male patients with immune complexes. It is suggested that extra-articular disease represents a manifestation of severe classical rheumatoid arthritis and is not an 'overlap' syndrome. We propose that the HLA haplotype Cw3-Bw62-Dw4-DR4-DRw53 makes a greater genetic contribution to disease susceptibility in both extra-articular and male rheumatoid arthritis patients than in other subsets of RA.

Arthritis, Rheumatoid↗

Histocompatibility testing in patients with carcinoma of the bladder.

A number of disease states have been found to have a positive association with certain HLA antigens. Weak associations have been described for a number of cancers. Seventy patients with transitional cell carcinoma of the bladder underwent serotyping for HLA, A, B, C, and DR antigens. There were 54 men and 16 women patients with a mean age of 65.3 years. Noninvasive lesions (Ta and T1) were present in 50 and 20 were invasive (T2, T3, and T4). Low grade tumors (G1 and G4) were found in 53 and 17 were moderately or poorly differentiated (G3 and G4). Gene frequencies for the HLA determinants in the cancer patients were compared to those for normal English caucasoids. No significant differences were found at either the A, B, C, or DR loci. DR4 was the commonest antigen expressed in bladder cancer patients with an allelic frequency of 39% compared to 28% in the normal population. The presence or absence of the DR4 antigen was not related to the stage or grade of the tumor.

Aged↗

Differential expression of HLA-DR and DR-linked determinants on human leukemias and lymphoid cells.

Leukemic and normal hemopoietic cells were examined with the monoclonal anti-bodies DA2 and Genox 353 for the presence of HLA-DR and DR-linked (DC/MB) determinants, respectively. Although most non-T acute leukemias and leukemic cell lines expressed the monomorphic DR determinant detected by DA2, fewer than expected expressed the DR-linked polymorphic specificity detected by Genox 353. TdT+ lymphoid precursors from normal bone marrow were also DA2+ but Genox 353-. T cells and thymocytes which were DA2-, Genox 353- became DA2+, Genox 353+ after activation in vitro. Immunoprecipitation using DA2 and Genox 353 gave bands on polyacrylamide gel-electrophoresis which were of different molecular weights. In addition, DA2 could absorb out Genox 353 determinants from a cell lysate whereas Genox 353 could not absorb out DA2 determinants. It is concluded that DA2 and Genox 353 detect HLA-DR and DR-linked (DC1/MB1) determinants, respectively, and that these are differentially expressed on hemopoietic cells during differentiation.

Antibodies, Monoclonal↗