Search PubMed⌕ Search

Biomedical subjects

A C Wang

Publications and source records attributed to A C Wang.

At least 73 records · Page 4Linked to original sources
PubMed1983

Some T-cell leukemia lines express surface markers related to a restricted set of human VH determinants.

Serological studies were carried out to obtain information regarding the relationship of the VH-related determinants expressed by certain permanent in vitro T-cell leukemia lines and corresponding determinants expressed by characterized human serum immunoglobulins. A panel of conventional (goat and rabbit) antisera, produced against various Fab-related fragments of monoclonal human Waldenstrom macroglobulins and polyclonal IgG molecules, bound to certain in vitro T-cell leukemia lines, notably, 70-N2, MT-1, YT4E, and HUT78, as shown by microhemagglutination. Inhibition studies using characterized myeloma proteins to inhibit this agglutination indicated the expression of a restricted VH-related determinant by these T-cell lines. Parallel studies performed using conventional (rabbit) and murine monoclonal/hybridoma antibodies produced against the isolated 68,000-Da VH-related product synthesized by the 70-N2 line showed that the determinant expressed by this molecule was restricted in expression, comprising 2-3% of the normal, polyclonal human Fab pool, and that the determinants found on the other positive T-cell leukemias were cross-reactive rather than identical. The inhibition studies suggest that the determinant resides between residue 22 and the end of the VH region. These results further define the antigenic nature of the VH-related marker found on the surfaces of certain normal and neoplastic T-cell lines.

Animals↗
PubMed1983

Existence of disulfide-bonded IgM-IgA, IgM-IgG and IgM-IgG fragment complexes in one patient.

The existence of disulfide-bonded immunoglobulin (Ig) complexes of IgM-IgA, IgM-IgG, and IgM-IgG, in addition to a monoclonal IgM (kappa) paraprotein, free kappa chains and fragments of IgG (FIgG), were found in the plasma of a multiple gammopathy patient. This is the first report on the interclass disulfide-bonded Ig complexes. Upon exposure to a dissociating buffer containing 6 M urea, 0.1 M Tris-HCl, pH 8.0, a small portion of the IgM-IgA complexes and most of the IgM-IgG as well as the IgM-FIgG complexes dissociated, but the majority of the IgM-IgA and small amounts of other complexes remained intact. These intact complexes were not the result of antigen-antibody reactions and were apparently held together by disulfide bonds which could be broken into monomeric Ig basic units (H-L)2 and smaller components by mild reduction and alkylation.

Disulfides↗
PubMed1983

Cytotoxic effect of anti-idiotype antibody-chlorambucil conjugates against human lymphoblastoid cells.

The secreted IgMs of two human lymphoblastoid cell lines, RPMI-6410 and RPMI-8392, were purified. Antisera against these two IgMs were raised in rabbits and made idiotypically specific to the respective antigens through various absorption procedures. By immunofluorescence and radioimmunoassay techniques, the purified anti-idiotype antibodies were found to react also with the membrane Igs of the respective cell lines, but not with those of other cell lines. The purified anti-idiotype antibodies were then coupled with Chlorambucil to form antibody-drug conjugates, whose effectiveness in the in-vitro killing of target cells was evaluated by a chromium-release cytotoxicity assay. The results showed that these anti-idiotype antibody-Chlorambucil conjugates were specifically cytotoxic to lymphoblastoid cells that bore membrane Igs carrying the respective idiotypic determinant(s). Furthermore, the conjugates were far more effective in causing cytolysis to the target cells than either Chlorambucil or the anti-idiotype antibodies alone.

Antibody Specificity↗
PubMed1982

Molecular basis for the temperature-dependent insolubility of cryoglobulins--XI. Sequence comparison of the heavy-chain variable regions of the human cryoimmunoglobulins McE and Hil by metric analysis.

The amino acid sequences of the VH-domains from two human cryoimmunoglobulins have been compared with one another and with the VH-domains of noncryoglobulins by the mathematical method of metric analysis. The VHII sequence of McE [Gerber-Jenson et al. (1981), J. Immun. 126, 1212-1216] and the VHIII sequence of Hil [Chiu et al (1979), Biochemistry, 18, 553-560] resemble much more closely the VH-sequences of noncryoglobulins from their own subgroups than they resemble one another. Neither cryoglobulin sequence contains an unusual insertion or deletion of residues. Based on the crystallographic structure of the VHII domain in the Fab fragment of the human noncryoglobulin Newm [Saul et al. (1978), J biol. Chem., 253, 585-597], McE and Hil each contain two unprecedented residues in the outer beta-sheet structure of the VH-domain. The inwardly directed sidechains of Gly-71 and Ile-84 in McE may perturb the internal hydrophobic interactions and normal folding of adjacent segments of the outer beta-sheet from the third framework region. In contrast, the outwardly directed sidechains of Ile-23 and Arg-77 in Hil may perturb the external hydrophilic properties and folding of adjacent segments of the outer beta-sheet from the first and third framework regions. Thus, the monoclonal immunoglobulins McE and Hil may display cold-induced insolubility by different perturbations of the outer surface of the VH-domain. In each case, the unprecedented framework residues that mnay be responsible could have arisen by two point mutations involving single base changes.

Amino Acid Sequence↗
PubMed1982

Molecular comparison of mouse Thy-1 and its human homologue.

Physicochemical techniques were used to verify previous immunochemical studies showing homology of the human Thy-1 (formerly p25) antigen and the murine Thy-1 or theta antigen. Peptide maps and amino acid compositions showed close similarity between these two proteins; however, they were not identical. These data confirm that the p25 antigen is the human homologue of mouse Thy-1.

Alanine↗
PubMed1982

Antigenic polypeptide fragments of a receptor related to the Fab fragment of human immunoglobulin from thymus-derived lymphocytes.

Certain thymus-derived lymphocytes of man and other primates express surface components related to the variable region of immunoglobulin heavy chains but lack constant region determinants defining any known immunoglobulin class. To obtain structural information on this molecule that can be used for comparison with known immunoglobulins and other surface molecules, we isolated the T cell-derived molecule by affinity chromatography using an antiserum raised against the monomeric Fab fragment of a human Waldenström macroglobulin and subjected the isolated molecule to either proteolysis using enzymes or cleavage with cyanogen bromide, followed by isolation of polypeptides which bore the Fab- or heavy chain variable region (VH)-related antigenic markers. The intact T cell molecule had an apparent mass of 68,000 daltons and no evidence was found for covalent or noncovalent association with polypeptides resembling light chains in apparent mass. The pattern of fragments obtained by cleavage of the T cell heavy chain suggests that the molecule is comprised of domains of approximate mass 12,000 daltons. Isolation of fragments from the digests that bear Fab-related serological markers shows that the molecule can be degraded into fragments resembling the Fd and VH of standard immunoglobulin heavy chains. A procedure was developed enabling the isolation of milligram quantities of VH-related T cell products. These results support the concept of a sharing of combining site determinants between T cell receptors and immunoglobulin heavy chains and show a general formal similarity between the two classes of molecules, even though they lack shared constant region determinants. The susceptibility of the T cell molecule to be cleaved into discrete antigenic fragments by controlled proteolysis might help to explain the plethora of sizes observed for antigen-specific T cell factors.

Animals↗
PubMed1982

Coexistence of multiple monoclonal immunoglobulins with identical constant regions in one patient.

Two populations of IgG molecules, designated F-IgG3(chi) and S-IgG3(chi), were isolated from a patient with multiple myeloma. The constant regions of the two molecules appear to be identical, since the heavy chains of both belong to the gamma 3 subclass and both molecules are positive for G3m(5), G3m(10), and G3m(11) but negative for G3m(21), Km(1) and Km(2) allotypes. In contrast, the two molecules have different variable regions, since (a) they do not share idiotypic determinant(s); (b) their light chains have different NH2 terminal amino acid sequences, and (c) both their heavy and light chains have different peptide maps and amino acid compositions. SDS-polyacrylamide gel electrophoresis showed that the F-IgG3(chi) molecules have two kinds of light chains. One, designated, chi n, has a normal molecular weight (approximately 23,000); the other, designated chi h, has a molecular weight of approximately 28,000.

Aged↗
PubMed1982

Serological and biochemical analyses of M components in patients with transitional cell carcinoma of the urinary bladder.

Serological and biochemical studies were performed on M components isolated from 3 patients with transitional cell carcinoma of the urinary bladder (TCC). All were IgG1(K) proteins. 2 of the 3 belonged to the VKI subgroup, and these 2 also possessed cross-reactive idiotypic determinants. These findings are consistent with the ideas that M components in patients with a given kind of cancer may have restricted heterogeneity, and that the synthesis of an M component and the manifestation of a solid tumor may be related events in some patients who exhibit both abnormalities.

Amino Acid Sequence↗
PubMed1982

Three M components IgA lambda, + IgG kappa n + IgG kappa h in one patient. II. Structurally different kappa n and kappa h chains associated with H(gamma) chains sharing idiotypic determinants.

Structural analysis of purified IgG kappa h and IgG kappa n molecules of DA myeloma paraproteins indicated that the two IgG had different electrophoretic mobility and that L-kappa h had an unusually heavy m.w. (30,000). Peptide mapping showed the existence of additional peptides in the L-kappa h map when compared to the L-kappa n map. Total amino acid analysis showed that L-kappa h contained two additional cysteine residues and certain other amino acids than L-kappa n contained. Sequence of the first 25 NH2-terminal amino acids showed differences at positions 4, 5, 15, 18, and 21, but both L-kappa h and L-kappa n belong to the same V kappa IV subgroup. IgG kappa n but not IgG kappa h reacted with anti-gamma 1 antiserum, indicating that H chains of these two paraproteins were also different. Sera from rabbits immunized with IgG kappa n or IgG kappa h, and rendered specific for idiotypic determinants by appropriate absorption, were used for idiotype characterization of these components. Immunodiffusion, immunoelectrophoresis, and direct hemagglutination demonstrated that IgG kappa h and IgG kappa n cross-reacted partially. Inhibition tests disclosed that the main anti-idiotypic antibody was directed against a conformation structure of the complete IgG kappa h molecule, whereas cross-reaction was due to partial idiotypic similarity between H chains of the IgG kappa h and IgG kappa n. In addition, each of these paraproteins seemed also to bear private idiotypes on their H and L chains.

Amino Acids↗
PubMed1981

A marmoset T-lymphocyte protein related to defined human serum immunoglobulin and fragments.

Current concepts of the antigen-specific receptor of thymus-derived (T) lymphocytes suggest that this molecule bears immunoglobulin (Ig) variable (V) regions, but does not represent a classical serum antibody. We immunized rabbits with a globulin fraction obtained from an in vitro cultured marmoset T cell lymphoma line which expressed surface components related to immunoglobulins. Quantitative immunoprecipitation and competition radioimmunoassay studies carried out using characterized monoclonal human Igs and their chains and fragments show that this rabbit antiserum, raised against a T cell product, reacts with a particular, conformational VH-determinant which is formed by interaction with lambda light chains and with two mu chain (IgM) related determinants. Neither mu chain determinant is a major isotype specific marker, and each occurs only on certain distinct subsets of serum mu chains. One is located in the Fc fragment; the location of the other mu related determinant is not known. These results show that this rabbit antiserum recognizes both variable and constant region determinants on the T cell receptor heavy chain. Rabbit antibody to the T cell product which cross-reacts with serum mu chain was isolated by immune affinity chromatography on Sepharose-derivatized covalently with one particular reactive IgM protein, the Waldenstrom macroglobulin Can (kappa mu). This antibody precipitated a biosynthetically-labelled component of approximate M.W. 70,000 as assessed by polyacrylamide gel electrophoresis in Na Dod SO4-containing buffers. These data support the conclusion that certain T cells express and synthesize a molecule related to Ig VH-regions which also has a constant region sharing antigenic markers with IgM subpopulations.

Animals↗
PubMed1981

Three monoclonal immunoglobulins, an IgG2(kappa), an IgM(kappa) and an IgM/A hybrid, in one patient. II. Sharing of common variable regions.

Amino acid sequencing and haemagglutination inhibition studies were performed on three monoclonal immunoglobulins (an IgG2, an IgM and an IgM/A hybrid) isolated from a patient afflicted with a multiple gammopathy. The results demonstrated that all three proteins have shared idiotypic determinant(s). Furthermore, the light chains of all three paraproteins have identical NH2-terminal amino-acid sequences at all positions determined thus far. Similarly, the NH2-terminal amino-acid sequence of the gamma 2 chains is identical to that of the mu chain. The evidence strongly suggests a common ancestral clonal origin for cells which produce these paraproteins and that identical variable region (VH and VL) genes were used by the ESM lymphocyte subclones in the biosynthesis of the respective IgM, IgG, and IgM/A hybrid molecules. The occurrence of a mu/alpha hybrid chain, which shares identical V regions with a mu and a gamma chain, is consistent with the concept that IgM-producing cells can develop directly into cells producing other classes of immunoglobulins via separate pathways during B-cell maturation.

Aged↗