Antibody modulation of antigen presentation: positive and negative effects on presentation of the tetanus toxin antigen via the murine B cell isoform of FcgammaRII.
Tetanus toxin has been a valuable model antigen to study the MHC class II-restricted antigen processing pathway and is also frequently used to provide T helper determinants in vaccine formulations. To date most basic studies on the processing of this antigen have utilized human T and B cell clones. As a first step towards extending studies on this antigen into the murine system we have generated a panel of T cell clones and mAb in H-2(b) and H-2(d) mice. We investigated the presentation of tetanus toxin C fragment (TTCF) by the murine B cell lines LB27.4 (H-2(dxb)), A20 (H-2(d)) and IIA1.6 (H-2(d)) and the extent to which this could be modulated by the addition of mAb. One mAb, 10G5, induced strikingly enhanced presentation of T cell determinants located in the N-terminal region of TTCF while other antibodies inhibited presentation of these and other epitopes. The enhancing effects of the 10G5 antibody were blocked by the anti-FcR antibody 2.4G2 and were not observed in the FcR-negative IIA1.6 cell line. Interestingly, both FcgammaRIIB1 and FcgammaRIIB2 isoforms of FcgammaRII were able to restore antibody enhanced presentation in IIA1.6 cells but only if the cytoplasmic tails were intact. These results show that the B cell isoform of FcgammaRII (FcgammaRIIB1) can mediate capture and presentation of some antigen/antibody complexes and might play a role in BCR-independent antigen presentation in vivo.
Antoniou
Antony N
AN
Division of Cell Biology and Immunology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, GB. a.n.antoniou@dundee.ac.uk
Watts
Colin
C
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D023302:Protein Footprinting; D020033:Protein Isoforms / Q000378:metabolism; D017452:Receptors, IgG / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D013744:Tetanus Toxin / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D020033:Protein Isoforms; D017452:Receptors, IgG; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C