TY - JOUR
T1 - Antibody modulation of antigen presentation
T2 - positive and negative effects on presentation of the tetanus toxin antigen via the murine B cell isoform of FcgammaRII
AU - Antoniou, Antony N
AU - Watts, Colin
PY - 2002/2
Y1 - 2002/2
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Animals
KW - Antibodies, Monoclonal
KW - Antigen Presentation
KW - B-Lymphocytes/immunology
KW - Cell Line
KW - Humans
KW - Mice
KW - Molecular Sequence Data
KW - Peptide Fragments/chemistry
KW - Protein Footprinting
KW - Protein Isoforms/metabolism
KW - Receptors, IgG/chemistry
KW - T-Lymphocytes/immunology
KW - Tetanus Toxin/chemistry
U2 - 10.1002/1521-4141(200202)32:2<530::AID-IMMU530>3.0.CO;2-X
DO - 10.1002/1521-4141(200202)32:2<530::AID-IMMU530>3.0.CO;2-X
M3 - Article
C2 - 11828370
VL - 32
SP - 530
EP - 540
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 2
ER -