Biomedical subjects

B Parhami-Seren

Publications and source records attributed to B Parhami-Seren.

25 records · Page 2Linked to original sources

PubMed1989

The amino acid residues at the VH-D-JH junctions affect the affinity of anti-p-azophenylarsonate antibodies.

Murine A/J anti-p-azophenylarsonate (Ars) antibodies sharing a predominant idiotype are encoded by a single combination of germ-line V region gene segments. The dominance of this idiotype among secondary immune response anti-Ars antibodies has been explained by the Ag-driven selection of favorable somatic mutants of this gene segment combination, associated with an intrinsic Ars-affinity of the germ-line V region higher than that of other possible combinations. To determine the effect of junctional diversity upon affinity for Ag, independently of somatic mutation, we determined the V region sequences and affinity for Ars of five primary response antibodies. These antibodies share identical unmutated V regions but differ only at the D gene junctions. Among the five antibodies, Ars-affinity differed up to 10-fold depending upon the identity of the amino acid residues at the VH-D and the D-JH junctions. The combination of junctional residues observed in two primary response antibodies with relatively low Ars-affinity has not been observed among secondary response antibodies. Thus the identity of junctional residues resulting from gene rearrangement prior to antigen stimulation must be taken into account in hypotheses which account for idiotype dominance by selection on the basis of affinity.

Amino Acid Sequence↗

PubMed1987

Somatically mutated forms of a major anti-p-azophenylarsonate antibody variable region with drastically reduced affinity for p-azophenylarsonate. By-products of an antigen-driven immune response?

The pivotal role played by antigen in the clonal selection of B cells for initial participation in an immune response is well established. Antigen selective mechanisms ensure that antigen-binding antibodies are produced during all stages of the immune response. However, antibodies that lack specificity for the immunogen might also be produced during the course of an antigen-driven immune response . It has been suggested that, through idiotype-antiidiotype network interactions within the immune system, production of antibodies that lack specificity for the immunogen but that share idiotopes with antigen-binding antibodies could result (1). In addition, data obtained by a number of investigators suggest that somatic mutation of antibody V region genes occurs at a rate of 10(-3)/basepair/cell division in B cells participating in an immune response (2, 3). One outcome of such V region structural alteration could be antibodies that lack, or have drastically reduced affinity for the immunogen . We sought to identify and characterize some of the antibody by-products of the antigen-driven immune response that are expected to be created by the mechanisms described above.

Amino Acid Sequence↗

PubMed1985

Preparation and characterization of monoclonal antibodies specific to placenta ferritin.

Ferritins are a group of isomeric proteins which function as the major iron-storage protein of mammalian tissues. Some of the isoferritins have low isoelectric points, and are found in placenta and in malignant tissues and have therefore been termed carcinofetal ferritins. With the use of hybridoma technology, monoclonal antibodies (McAbs) specific to human placenta ferritin(s) were produced in order to characterize the heterogeneity of the molecule and to answer the question whether a specific antigenic determinant is associated with placenta and/or carcinofetal ferritin(s). Two McAbs designated H-9 and G-8 were developed. McAb H-9 bound specifically and exclusively to the ferritin isolated from human placenta, whereas G-8 McAb bound to placenta ferritin and cross-reacted with ferritins isolated from human spleen and liver. No cross-reaction was observed between H-9 and G-8 reactive determinants. It was found further that the two antigenic determinants - the one recognized by G-8 and that recognized by H-9 McAbs - are molecularly associated on placenta ferritin. The results of this study led us to term the G-8 a 'common' ferritin antigenic determinant and H-9 a 'private' embryonic ferritin determinant.

Animals↗

PubMed1984

Serological analysis of idiotypic determinants on monoclonal antibodies specific to poly(Tyr,Glu)-poly(DLAla)--poly(Lys) and its ordered analogue (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys).

Anti-idiotypic sera (aIds) were raised in C57BL/6 mice against monoclonal antibodies (McAbs) which bind poly(Tyr,Glu)-poly(DLAla)--poly(Lys)--abbreviated to (T,G)-A--L--and (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys)--abbreviated to (T-T-G-G)-A--L--(nos. 103 and 160) and McAbs which react only with (T-T-G-G)-A--L (nos. 100 and 114). Anti-Id antibodies against 103 McAb reacted with (T,G)-A--L specific antibodies and specifically inhibited their binding to iodinated antigen. Similarly, conventional antibodies against the major idiotypes of (T,G)-A--L-specific antibodies inhibited the binding of 103 McAb to antigen. It is therefore suggested that 103 McAb shares major idiotypes with (T,G)-A--L-specific polyclonal antibodies of C3H.SW origin. Anti-Ids against 114 McAb also inhibited the binding of (T,G)-A--L-specific antibodies to antigen, but the binding of 114 McAb could not be inhibited by conventional aIds. Therefore, idiotypes of 103 and 114 McAbs define idiotypic determinants expressed on two different subpopulations of (T,G)-A--L-specific antibodies: those that carry major idiotypes and those which express idiotypic determinants other than the major one (minor Ids). Anti-idiotypic sera against McAbs nos. 100 and 160 reacted with the homologous idiotypes and not with the major idiotypes of (T,G)-A--L-specific antibodies. In addition to the aforementioned specificities we could define cross-reactive idiotypes (private) shared by McAbs nos. 100, 103 and 114 McAbs nos. 160 and 114. The analysis of idiotypes expressed on anti-(T,G)-A--L McAbs enabled the detection of new antigen binding site related idiotypic determinants in addition to the major idiotypes which were immunodominant in the polyclonal anti-(T,G)-A--L antibodies.

Animals↗

PubMed1983

Fine specificity of antibodies to the synthetic polypeptide poly(L-tyrosine, L-glutamic acid)-poly(DL-alanine)--poly(L-lysine) and its ordered analogs as followed by solid-phase radioimmunoassay.

The fine specificity of antibodies against (T,G)-A--L and its ordered analogs (T-T-G-G)-A--L and (T-G-T-G)-A--L was studied. Fifty percent of the antibodies against (T,G)-A--L are directed toward the T-T-G-G determinants and 19% against T-G-T-G-like determinants. The rest of the antibody response to (T,G)-A--L is directed against determinants which exist in (T,G)-A--L but are not cross-reactive with either T-T-G-G- or T-G-T-G-like determinants. Although (T-T-G-G)-A--L and (T-G-T-G)-A--L differ only in the sequence of tyrosine and glutamic acid in their side chains, no crossreactivity was observed between antibodies toward the two ordered polypeptide antigens.

Animals↗

PubMed1983

Fine specificity and idiotypic expression of monoclonal antibodies directed against poly(Tyr,Glu)-poly(DLAla)--poly(Lys) and its ordered analogue (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys).

In order to study the repertoire of poly(Tyr,Glu)-poly(DLAla)--poly(Lys) [(T,G)-A--L] specific antibodies, monoclonal antibodies were prepared by fusing myeloma cells with spleen cells from C3H.SW mice immunized with (T,G)-A--L and boosted with (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys)](T-T-G-G)-A--L]. Eleven clones which secreted homogeneous antibodies were obtained. In general, two families of monoclonal antibodies were detected: those which bind exclusively (T-T-G-G)-A--L and those which bind both (T-T-G-G)-A--L and (T,G)-A--L. Analysis for idiotypic expression revealed that only two antibodies (clones no. 103 and 160), which were found to be similar in their fine specificity, cross-reacted with antibodies against the major idiotypes of (T,G)A--L specific antibodies. Guinea-pig antibodies against clone no. 160 reacted with the polyclonal (T,G)-A--L specific antibodies, whereas antibodies against 103 monoclonal antibodies did not react with C3H.SW anti-(T,G)-A--L antibodies, but did cross-react with four other monoclonal antibodies. It appears that the idiotypic determinants expressed on polyclonal (T,G)-A--L specific antibodies are heterogeneous, and consist of at least two serologically different idiotypes detected by clones no. 103 and 160.

Animals↗

PubMed1982

Cellular analysis of specificity of antibodies and of delayed type hypersensitivity responses toward some structurally related synthetic antigens: boosting is determined by specificity of T cells.

The crossreactivity between the random synthetic polypeptide antigen poly(Tyr,Glu)-poly(DLAla)--poly(Lys) [(T,G)-A--L] and its ordered-sequence analogs (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys) [(T-T-G-G)-A--L] and (Tyr-Glu-Tyr-Glu)-poly(DLAla)--poly(Lys) [(T-G-T-G)-A--L] at the level of humoral and cellular responses was studied. For delayed type hypersensitivity responses, (T,G)-A--L-activated T cells could be challenged with the homologous antigen as well as with the ordered analogs. T cells activated by (T-T-G-G)-A--L could be challenged with either the homologous antigen or with (T,G)-A--L but not with (T-G-T-G)-A--L. Similarly, no cross stimulation was observed between (T-G-T-G)-A--L-activated cells and (T-T-G-G)-A--L, whereas (T,G)-A--L could challenge the latter cells to mediate significant responses. Similar but not identical cross reactions were observed when primed spleen cells or lymph nodes were transferred to irradiated recipients that were boosted for the production of antibodies. In contrast to observations at the level of cellular responses, (T-G-T-G)-A--L-primed spleen or lymph node cells could not be boosted with (T,G)-A--L for the production of detectable amounts of antibodies, although boosting with the homologous antigen resulted in significant levels of (T-G-T-G)-A--L-specific antibodies. Transfer experiments in which mixtures of T and B cells, each primed to a different ordered polypeptide antigen, were injected into irradiated recipients showed that successful cooperation occurs provided that the boost is given with the T-cell-specific antigen. The antibodies produced were specific to the antigen used for B-cell priming. The T-cell-B-cell collaboration probably occurs through specific determinants that are shared between the two antigens in which the ordered peptides are attached to the same multichain polymer and that are recognized by both the T and the B cells.

Amino Acid Sequence↗