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Biomedical subjects

D L Mann

Publications and source records attributed to D L Mann.

At least 217 records · Page 12Linked to original sources
PubMed1981

Human B-cell alloantigens DC1, MT1, and LB12 are identical to each other but distinct from the HLA-DR antigen.

Some human B-lymphoblastoid cell lines are shown to express at least two types of Ia-like antigens. One antigen is defined by alloantisera to HLA-DR, and the other antigen is defined by alloantisera and a monoclonal antibody to the specificities DC1, MT1 (MB1), and LB12, which are in linkage disequilibrium with HLA-DR. The subunits of the DC1 molecule differ from those of the DR molecule. The light chains of both molecules are structurally polymorphic.

B-Lymphocytes↗
PubMed1981

Characterization of a monoclonal antibody (5E9) that defines a human cell surface antigen of cell activation.

This study describes the monoclonal antibody 5E9 and the cell surface antigen it defines. The hybridoma cell line T3-5E9 was derived from fusion of P3 X 63/Ag8 myeloma cells and spleen cells from BALB/c mice immunized with HSB-2 cells, a human T cell line. Although binding to only 1 to 5% of peripheral blood (PB) and spleen mononuclear cells, 5E9 antibody bound to 40 to 80% of Con A-, PHA-, or PWM-activated PB cells. Moreover, 5E9 antibody bound to variable numbers of Sezary, acute myelogenous leukemia, and ALL PB leukemia cells. 5E9 antibody bound to all hematopoietic and nonhematopoietic cell lines tested, to 11 +/- 1% of thymocytes, and 40% of nucleated bone marrow cells. Under reducing conditions, immunoprecipitation studies using 5E9 antibody demonstrated 5E9 antigen to be an 90,000 m.w. glycoprotein. Under nonreducing conditions, antigen 5E9 is a disulfide-linked dimer of approximately 190,000 daltons. Sequential precipitation experiments using antibody 5E9, alpha OD heteroantiserum (raised against T ALL cells), and monoclonal antibody OKT9 demonstrated that the 3 antibody preparations recognized the same 90,000 m.w. glycoprotein. Thus, antibody 5E9 defines an 90,000 m.w. human cell surface antigen that is absent on the majority of PB mononuclear cells and is expressed on rapidly dividing normal and malignant human cells. This monoclonal antibody should be a useful marker of human cell activation.

Animals↗
PubMed1980

Participation of suppressor T cells in the immunosuppressive activity of a heteroantiserum to human Ia-like antigens (p23,30).

We studied the effects of an antiserum to human Ia-like antigens (p23,30) upon the polyclonal activation of normal B cells (cultured with various combination of irradiated and unirradiated T cells) to become immunoglobulin-secreting cells after stimulation with pokeweed mitogen in vitro. We found that the antiserum suppressed immunoglobulin production. The inhibitory effect did not appear to result from a simple interaction at the B-cell/monocyte level alone. Rather, the inhibitory effect required the presence of a radiosensitive subset of autologous suppressor T cells.

Animals↗
PubMed1980

Characterization of a monoclonal antibody that defines an immunoregulatory T cell subset for immunoglobulin synthesis in humans.

This study characterizes a monoclonal antibody (3A1), and partially characterizes the cell surface antigen and the functional peripheral blood T cell subset that it defines. The 3A1 antigen is present on the surface of several human T cell lines (HSB-2, CEM, MOLT-4, and others) in various amounts but is absent from the T cell line YT4E and all human B cell lines tested. Immunoprecipitation of an HSB-2 extract with 3A1 yielded one specific band with a molecular weight of approximately 40,000 in the presence of reducing agent. With directly fluoresceinated 3A1 antibody, fluorescence-activated cell sorter analysis showed that 85% of peripheral blood E-rosette-positive T cells were positive for the 3A1 antigen. After E-rosette-positive cells had been separated into 3A1+ and 3A1- cell suspensions, the 3A1+ cells helped autologous peripheral blood B cell suspensions toward pokeweed mitogen-driven proliferation and intracytoplasmic Ig production, whereas 3A1-T cells did not. Further, addition of 3A1- cells from some but not all normal subjects to cocultures of 3A1+ cells and B cells actively suppressed intracytoplasmic Ig production. However, the 3A1+T cell subset could be activated by concanavalin A to maximally suppress B cell Ig synthesis in vitro. Thus, the 3A1 antibody defines a major functional subject of peripheral blood T cells and should provide a useful marker for the study of human T cell function.

Antibody Formation↗
PubMed1980

An evaluation of the significance of amino acid sequence homologies in human histocompatibility antigens (HLA-A and HLA-B) with immunoglobulins and other proteins, using relatively short sequences.

A computer search was carried out for homologies between HLA-A and HLA-B antigen sequences and the sequences of constant and variable regions of immunoglobulins and of all other sequenced proteins. Searches were made both with relatively short peptide sequences from the HLA antigens and with those longer peptide sequences which were available in 1978. Significant homology of HLA antigen sequences to immunoglobulin constant region sequences was found in two cases: (1) a short decapeptide sequence which includes the fourth cysteine residue of HLA-B7 and (2) an 89-amino-acid residue (Ac-2) C-terminal fragment of the papainsolubilized HLA-B7 molecule. The difficulty of establishing statistically significant sequence homology with relatively short peptide sequences is emphasized by computer-based comparisons of the decapeptide sequence with randomly generated peptide sequences. It is concluded that statistically significant homology with short sequences can be assured only when extraordinarily high degrees of homology are present and additional constraints are included in the matches, for example, matches at relatively rare amino acid residues such as Cys, His and Trp. The homology of the 89-amino-acid residue sequence to constant region sequences of immunoglobulins is as great as or greater than that of beta 2-microglobulin. These findings and the unique domain structure involving a disulphide loop of comparable size strongly favour a common evolutionary origin for this region of HLA-A and -B, beta 2-microglobulin and immunoglobulin constant regions.

Amino Acid Sequence↗
PubMed1980

Histocompatibility alloantigens in psoriasis and psoriatic arthritis. Evidence for the influence of multiple genes in the major histocompatibility complex.

The frequency of HLA-A, B, and Cw antigens as well as the antigens expressed preferentially on B cells and monocytes (DRw and Ia-like) was examined in a normal population and two related disease populations, psoriasis and psoriatic arthritis. HLA antigens distinguishing the two disease populations were found. Psoriatic patients demonstrated an increase in frequency of HLA-A1, B17, and B13. Patients with psoriatic arthritis demonstrated an increased frequency of HLA-A26, B38, and DRw4. Antigens showing a common increase in frequency in the two disease populations were HLA-Cw6, DRw7, and Ia744. These results demonstrate genetic differences as well as similarities in the two populations of patients with the common clinical feature of psoriasis. In addition to the above analysis, we examined the association of individual alloantigens elevated in frequency in the diseased population. These same alloantigens were examined for association in the normal population. This analysis revealed HLA antigen associations in the two disease groups that differed from the association of several antigens in the normal population. The results suggest that at least two genetic factors, one mapping in the HLA-A, C-B region and one mapping in the HLA-B-DRw region are associated with the disease states. Thus, multiple factors controlled by genes in the major histocompatibility complex appear to contribute to the disease entities under investigation.

Arthritis↗
PubMed1980

Sjögren's syndrome (Sicca syndrome): current issues.

This paper outlines the clinical, serologic, and immunogenetic differences and similarities of Sjögren's syndrome alone (primary) and Sjögren's syndrome associated with rheumatoid arthritis and systemic lupus erythematosus (secondary). The immunoregulation in Sjögren's syndrome is discussed and the incidence of immune complex-like material, its nature, pathophysiology, and clearance by the Fc recptor of the reticuloendothelial system presented.

Antigen-Antibody Complex↗
PubMed1980

Waldenström's macroglobulinemia and autoimmune disease in a family.

We diagnosed Waldenström's macroglobulinemia in a father and three offspring. Clinical and subclinical autoimmune disorders occurred excessively in the family. The HLA haplotype A2, B8, DRw3 was detected in all patients with Waldenström's macroglobulinemia and all but one family member with autoimmune manifestations. A lod score [log odds] of 4.86 favors linkage to the HLA complex of a gene predisposing to lymphoproliferative and autoimmune disorders. Associated with this HLA haplotype were the B-cell alloantigens Ia-172 and 350, previously reported in patients with the lymphoma-prone sicca syndrome.

Adult↗
PubMed1980

HLA-DRw alloantigens can be detected on peripheral blood T lymphocytes.

Antisera detecting HLA-DRw antigens (human Ia-like) react in cytotoxicity assays with peripheral blood B cells and monocytes but not T lymphocytes. Antisera detecting DRw specificities were used in flow microfluorometry studies to determine whether T lymphocytes express these antigens in quantities not detected by cytotoxicity. Peripheral blood lymphocytes depleted of monocytes were incubated with DRw antisera, reacted with fluoresceinated goat anti-human IgG, and analyzed on the fluorescence-activated cell sorter (FACS). Anti-DRw sera were found to be reactive on all of the lymphocytes as evidenced by a positive fluorescence signal. The reactivity was specific in that only those sera that detected DRw antigens on B cells and monocytes were reactive with the total lymphocyte population from the same donor. Reactivity of the antisera was removed by absorbing the antiserum with monocyte/B cells and T cells from a donor with the same DRw antigen as that found on the target cell of the donor tested. The results demonstrate the presence of DRw antigens on resting peripheral blood T lymphocytes. The implications of quantitative differences in DRw antigen expression on lymphoid cells are discussed.

Absorption↗
PubMed1980

Inhibition of DRw antisera reactivity by mono and oligosaccharides.

Mono and oligosaccharides were used to inhibit the cytotoxicity of antisera detecting HLA-DRw antigens on monocytes isolated from peripheral blood. Certain sugars preferentially inhibited antisera detecting some DRw antigens and not others. Sera detecting HLA-A and B antigens were not inhibited with the sugars used. Anti-DRw sera blocked the attachment of radiolabeled sugars to monocytes with the same patterns as the reciprocal blocking of cytotoxicity by the sugars. The results were not consistent with the intrepretation that carbohydrates are an antigenic "component" of DRw specificity, but rather that the surface structures, possibly those bearing the DRw antigens, are receptors for mono and oligo saccharides.

Cellobiose↗
PubMed1979

Complete amino acid sequence of a papain-solubilized human histocompatibility antigen HLA-B7. 1. Isolation and amino acid composition of fragments and of tryptic and chymotryptic peptides.

As a part of the overall strategy for determining the complete covalent structure of the papain-solubilized portion of the heavy chain of the human histocompatibility antigen HLA-B7, the protein was dissected into various fragments by a combination of partial acid hydrolysis and cyanogen bromide cleavage. After purification by chromatographic procedures, these fragments have been used as a source for tryptic and chymotryptic peptides. Thirty-three major tryptic and twenty-two major chymotryptic peptides were purified in nanomole amounts and their amino acid compositions determined. These peptides account for the whole extent of the polypeptide chain with the exception of the amino-terminal CNBr pentapeptide. They provide the basis for the formal alignment of the acid cleavage and cyanogen bromide fragments of the molecule as well as the source material for the elucidation of the primary structure of the HLA-B7 heavy chain.

Amino Acid Sequence↗
PubMed1979

Studies on the contact sensitization of man with simple chemicals: V. Clonal priming allows direct in vitro assessment of autologous HLA-associated factors required for immune response to dinitrochlorobenzene.

Human lymphocytes from dinitrochlorobenzene (DNCB)-sensitized human subjects primed in first culture with dinitrophenylated-antigens yield a population of cells which respond in an accelerated manner to the same or similar antigen in second culture. Using this "clonal priming" approach, we have demonstrated that such a primed population showed maximal proliferative response to dinitrophenylated autologous cells. These DNP primed clones also showed responses to some dinitrophenylated allogeneic leukocytes. The magnitude of the accelerated blastogenic response with allogeneic leukocytes varied in most instances in relation to the degree of sharing of HLA-A, B, and DRw antigens with the original autologous stimulator. These findings show that the self-specific factors recognized in conjunction with the dinitrophenyl antigen are closely but not invariably associated with established major histocompatibility (MHC)-associated serologic typing results. While DNP primed clones fail to respond to unmodified autologous leukocytes, they often show significant responses to unmodified allogeneic leukocytes. If such accelerated responses to unmodified allogeneic leukocytes are not the result of nonspecific activation of allogeneic responding lymphocyte clones, these findings further indicate that DNP modified self can resemble some alloantigens.

Dermatitis, Contact↗
PubMed1979

Sharing Ia antigens between species. III. Ia specificities shared between mice and human beings.

Certain mouse alloantisera have been found to detect immunologic cross-reactions between human and murine Ia antigens. Almost every anti-Iaa, -Iak and -Iad serum tested exhibited such cross-reactions. Sera prepared against the products of limited segments of the mouse I region and tested on human B cells revealed that anti-I-E/Ck cross-reactions were more readily detectable than anti-I-A, B, Jk cross-reactions. Most of the mouse alloantisera were cytotoxic to bells from almost every individual tested, although a few sera exhibited more restricted patterns of lysis, permitting limited segregation analyses. The cytotoxicity of these mouse alloantisera in family studies was consistent with HLA linkage of the genes responsible for the cross-reacting Ia determinants. Immunochemical analysis on radiolabelled detergent lysates of human lymphocytes indicated that the sera reacted with molecules of 34,000 and 28,000 daltons. Thus, by cellular distribution, HLA association, and immunochemical criteria, these mouse alloantisera detect human Ia antigens. These cross-reactive sera should be of practical value for the detection of human Ia antigens and may also have theoretical implications for the evolution of genes coding for Ia antigens.

Animals↗
PubMed1979

Human B-cell antigens in acute lymphocytic leukemia. Lack of correlation with other lymphocyte surface markers.

Cells from patients with acute lymphocytic leukemia were studied for cell surface markers and B-cel alloantigens. Three cell types were defined. Those spontaneously rosetting with erythrocytes and not prossessing surface immunoglobulin or complement receptors were considered T-cells. Cells not showing rosette formation, surface immunoglobulin, or complement receptors were considered null cells and could be divided into two categories based on their ability to stimulate in mixed lymphocyte reaction. B-cell alloantigens were found randomly distributed on all cell types. The results suggested that genetic information for human B-cell antigens was present in all cell types and that other cell surface markers may reflect a stage of differentiation of the leukemia cell type.

Antigens, Surface↗