PubMed Health⌕ Search

Biomedical subjects

D W Metzger

Publications and source records attributed to D W Metzger.

60 records · Page 4Linked to original sources

Positive selection of major histocompatibility complex-restricted suppressor T cells bearing the predominant idiotype in the immune response to lysozyme.

The lysozyme system provides an excellent model for studying the role of multiple major histocompatibility complex (MHC) genes in the induction and regulation of Ir-gene controlled immune responses. Immunization of H-2b mice leads to concomitant activation of helper and suppressor activities by different epitopes on hen egg-white lysozyme (HEL) and thus phenotype unresponsiveness to native HEL. HEL-specific suppressor T cells in C57BL/10 nonresponder mice show MHC restriction, because their enrichment on antigen-pulsed macrophage monolayers requires syngeneic macrophages as well as HEL. The expression of the selected suppressor function requires interaction between the restricted suppressor precursor cell and an HEL-triggered, suppressor-inducer T cell. The MHC-restricted suppressor precursors bear the predominant idiotype found on anti-HEL antibodies, whereas MHC-restricted helpers do not.

Animals↗

Sharing of an idiotypic marker by monoclonal antibodies specific for distinct regions of hen lysozyme.

Idiotypes have been defined serologically as variable-region markers present on unique subsets of antibody molecules. Most studies involving myeloma proteins and antibody responses in inbred mice have indicated that idiotypy is closely related to antigenic specificity. However, indirect evidence suggests that idiotypy can sometimes be dissociated from specificity. In the response to the small monomeric protein, hen egg-white lysozyme (HEL), previous results demonstrated that 70--95% of the anti-HEL antibody found in sera of primed and boosted mice is specific for a particular region of HEL and bears a predominant idiotype (IdX-HEL). In this report, hybridoma anti-HEL antibodies tested with well-characterized peptide fragments of HEL show that the IdX-HEL marker can be found on antibodies of completely distinct antigen specificities. Thus, a mode of recognition other than antigenic recognition probably plays a major role in the immune response to HEL.

Animals↗

Group A streptococcal isolate 64/14 expresses surface plasmin-binding structures in addition to Plr.

A recombinant plasmin receptor (Plr) gene product originally cloned from group A streptococcal isolate 64/14 was analysed for its ability to bind plasmin(ogen) and to account for all the surface plasmin-binding properties of streptococcal isolate 64/14. Functional analysis of recombinant Plr demonstrated that the protein exhibited equal reactivity with human Lys-plasmin and Lys-plasminogen, but significantly lower reactivity with Glu-plasminogen. Plasmin-binding was both inhibitable and elutable by lysine or lysine analogs, and active plasmin bound to recombinant Plr was not neutralized by alpha 2-antiplasmin. Thus, the plasmin-binding properties of recombinant Plr correlated with the plasmin-binding phenotype of the intact streptococcal isolate 64/14. In addition, fluid-phase recombinant Plr could completely inhibit binding of plasmin to either immobilized recombinant Plr or group A streptococcal isolate 64/14 with equal efficiency, indicating that surface-expressed Plr could account for all the plasmin-binding properties of the intact organism. An IgM monoclonal antibody to recombinant Plr that specifically recognized a surface structure on streptococcal isolate 64/14 significantly inhibited the binding of plasmin to the recombinant protein; however, the antibody was not successful at inhibiting plasmin-binding to the intact bacteria, indicating the presence of other plasmin-binding structures on the bacterial surface in addition to Plr.

Animals↗