The immunoaugmenting properties of murine IgD reside in its C delta 1 and C delta 3 regions: potential role for IgD-associated glycans.
IgD receptor (IgD-R) bearing CD4+ T cells with immunoaugmenting properties in vivo are induced in mice within 24 h after a single injection of dimeric or aggregated IgD. In the present study, we sought to identify the region(s) of IgD responsible for upregulation of IgD-R and for the immunoaugmenting effect of IgD. IgD-R can be upregulated on CD4+ T cells in vitro and in vivo by glutaraldehyde-aggregated mutant IgD or by fragments of enzymatically digested IgD molecules possessing either the C delta 1 domain (Fd delta) or the C delta 3 domain (Fc delta). Neoglycoproteins (D-galactose--BSA and N-acetyl-D-glucosamine--BSA), can competitively block upregulation of IgD-R by IgD in vitro. Furthermore, when injected 1 day before antigen, the aggregated IgD derived molecules, KWD1 (which lacks C delta 1), KWD6 (which lacks C delta 1 plus C delta-hinge), and Fab delta can all cause augmentation of antigen-specific primary and secondary antibody responses comparable to that achieved with intact aggregated IgD. Moreover, the immunoaugmenting effect of intact oligomeric IgD molecules in primary antibody responses is competitively blocked by simultaneous injection of monomeric forms of KWD6 and Fab delta. These results suggest that the binding of IgD to IgD-R, previously shown to be dependent on N-glycans present on Fd delta and Fc delta regions, also contributes to the upregulation of IgD-R and immunoagumentation.
Amin
A R
AR
Department of Pathology, New York University School of Medicine, NY 10016.
Tamma
S M
SM
Swenson
C D
CD
Kieda
C C
CC
Oppenheim
J D
JD
Finkelman
F D
FD
Coico
R F
RF
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D007127:Immunoglobulin Constant Regions / Q000737:chemistry* / Q000378:metabolism; D007072:Immunoglobulin D / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000378:metabolism; D007138:Immunoglobulin delta-Chains / Q000737:chemistry* / Q000378:metabolism; D007136:Immunoglobulins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000378:metabolism; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D007127:Immunoglobulin Constant Regions; D007072:Immunoglobulin D; D007141:Immunoglobulin Fc Fragments; D007138:Immunoglobulin delta-Chains; D007136:Immunoglobulins; D011134:Polysaccharides; D011961:Receptors, Fc; D011971:Receptors, Immunologic; C050855:immunoglobulin D receptor