Search PubMed⌕ Search

Biomedical subjects

T R Mosmann

Publications and source records attributed to T R Mosmann.

101 records · Page 6Linked to original sources

Alteration of apparent specificity of monoclonal (hybridoma) antibodies recognizing polymorphic histocompatibility and blood group determinants.

The fine specificity of five mouse anti-chicken monoclonal antibodies was altered by changes in pH or temperature. Four of these antibodies recognized determinants of the MHC, and the fifth recognized another polymorphic erythrocyte antigen. The pH changes could alter a monoclonal antibody specificity from an apparently private determinant to an apparently public determinant. These alterations have been interpreted on the basis of the pH effect on binding affinity, relative to the threshold of the assay used. Consistent with this interpretation was the observation that bound antibodies were eluted most rapidly from a "cross-reacting" antigen, even at a pH where cross-reactions were strongest. Also, an increase in the valency of the monoclonal antibody resulted in an increase in the observed degree of cross-reaction. This was demonstrated in a highly multivalent antibody-directed rosette assay (ADRA), where the cross-reactions occurred over a wider pH range. These results have considerable importance for the use of monoclonal antibodies as monospecific reagents, especially in highly polymorphic systems such as the MHC. Also, these results suggest ways to improve the apparent specificity of particular monoclonal antibodies, e.g., by removing undesirable cross-reactions.

Animals↗

Mutations affecting immunoglobulin light chain secretion by myeloma cells. I. Functional analysis by cell fusion.

Two clones of MOPC 315 cells have been selected which synthesize but do not secrete Ig lambda light chains. These clones were analyzed by fusion with a cell line synthesizing and secreting kappa chains. Conditions were established for recovery at high frequency (approximately 10(-3)) of spontaneously fused, viable hybrid cells. The resulting hybrid cell lines synthesized both kappa and lambda chains but secreted only kappa chains. Hybrid cells produced by fusion of a lambda-secreting clone of MOPC 315 with the kappa-secreting cell line were also isolated and shown to synthesize and secrete both kappa and lambda chains. These results suggest that the nonsecretion of lambda chains was not due to a defect the secretion mechanism of the variant cells. A more likely alternative is that the lambda chains in the variant cell lines were structurally altered to a form which could not be secreted.

Animals↗

The ability of the murine placenta to absorb monoclonal anti-fetal H-2K antibody from the maternal circulation.

In previous work we have found that partially purified 125I-labeled anti H-2 antibody is localized in the placenta when injected i.v. into females pregnant by males bearing the target haplotype. This led to the concept that the placenta is an H-2 antigen-bearing immunoabsorbent barrier between mother and fetus. In this report we have used an anti-H-2Kk monoclonal antibody of the IgG2a subclass, also labeled with 125I, to verify this concept, as well as to improve the genetic definition of the immunoabsorbent antigen. In addition we have prepared F(ab')2 fragments of this antibody, and these also show the immunoabsorbent effect. This indicates that transport into fetally derived tissues via Fc binding is not a prerequisite for reaction of the antibody with paternal strain H-2 K antigens.

Absorption↗

Pigmentation and acriflavine resistance in Serratia marcescens.

Stable, orange, acriflavine-resistant variants were selected by treatment of a wild-type, red, acriflavine-sensitive strain of Serratia marcescens with acriflavine. Visible, ultraviolet, infrared, and nuclear magnetic resonance spectra of purified pigment from the red strain were identical to those of the pigment from the orange strain, and the orange mutant was not due to a mutation affecting the structure of the pigment, prodigiosin. The color of the red strain was not affected by variations in pH between 5.0 and 8.0, whereas the color of the orange mutant changed from pink to orange over the same pH range. This variation was mimicked by the pH-induced variation in color of prodigiosin purified from either the red, wild-type or the orange, mutant strains. Density-gradient centrifugation of cell fragments after ultrasonic disintegration resulted in characteristic pigmented bands. Biochemical characterization of these pigmented bands showed that they contained pigment and a protein component, but no lipids, polysaccharides, sugars, glucosamine, or phosphates were detected. Further fractionation of these pigmented bands by zone electrophoresis on a sucrose density gradient indicated that some pigment in S. marcescens was specifically attached to protein components.

Acridines↗