Abstract
Immunoglobulins drive efficient antigen capture by antigen presenting cells for processing and presentation on class II MHC-molecules. High affinity antibody/antigen interactions are stable at endosomal/lysosomal pH thus altering the substrate for antigen processing. We show that this can result in strong suppression of presentation of some T cell epitopes. This effect was observed when the antibody specificity was a B cell surface Ig, or formed part of an immune complex. In the latter case the presence of the suppressing antibody boosts presentation of other T cell epitopes through enhanced uptake into Fc receptor bearing cells. The influence of bound antibodies on the outcome of antigen processing may influence with T cell epitopes dominate T cell responses and may change the focus of the response with time.
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- Barnett B. C., Burt D. S., Graham C. M., Warren A. P., Skehel J. J., Thomas D. B. I-Ad restricted T cell recognition of influenza hemagglutinin. Synthetic peptides identify multiple epitopes corresponding to antibody-binding regions of the HA1 subunit. J Immunol. 1989 Oct 15;143(8):2663–2669. [PubMed] [Google Scholar]
- Barnett B. C., Graham C. M., Burt D. S., Skehel J. J., Thomas D. B. The immune response of BALB/c mice to influenza hemagglutinin: commonality of the B cell and T cell repertoires and their relevance to antigenic drift. Eur J Immunol. 1989 Mar;19(3):515–521. doi: 10.1002/eji.1830190316. [DOI] [PubMed] [Google Scholar]
- Berzofsky J. A. T-B reciprocity. An Ia-restricted epitope-specific circuit regulating T cell-B cell interaction and antibody specificity. Surv Immunol Res. 1983;2(3):223–229. doi: 10.1007/BF02918417. [DOI] [PubMed] [Google Scholar]
- Davidson H. W., Watts C. Epitope-directed processing of specific antigen by B lymphocytes. J Cell Biol. 1989 Jul;109(1):85–92. doi: 10.1083/jcb.109.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Demotz S., Lanzavecchia A., Eisel U., Niemann H., Widmann C., Corradin G. Delineation of several DR-restricted tetanus toxin T cell epitopes. J Immunol. 1989 Jan 15;142(2):394–402. [PubMed] [Google Scholar]
- Eisel U., Jarausch W., Goretzki K., Henschen A., Engels J., Weller U., Hudel M., Habermann E., Niemann H. Tetanus toxin: primary structure, expression in E. coli, and homology with botulinum toxins. EMBO J. 1986 Oct;5(10):2495–2502. doi: 10.1002/j.1460-2075.1986.tb04527.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eynon E. E., Parker D. C. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J Exp Med. 1992 Jan 1;175(1):131–138. doi: 10.1084/jem.175.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fairweather N. F., Lyness V. A. The complete nucleotide sequence of tetanus toxin. Nucleic Acids Res. 1986 Oct 10;14(19):7809–7812. doi: 10.1093/nar/14.19.7809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jemmerson R., Paterson Y. Mapping epitopes on a protein antigen by the proteolysis of antigen-antibody complexes. Science. 1986 May 23;232(4753):1001–1004. doi: 10.1126/science.2422757. [DOI] [PubMed] [Google Scholar]
- Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
- Lassila O., Vainio O., Matzinger P. Can B cells turn on virgin T cells? Nature. 1988 Jul 21;334(6179):253–255. doi: 10.1038/334253a0. [DOI] [PubMed] [Google Scholar]
- Manca F., Fenoglio D., Kunkl A., Cambiaggi C., Sasso M., Celada F. Differential activation of T cell clones stimulated by macrophages exposed to antigen complexed with monoclonal antibodies. A possible influence of paratope specificity on the mode of antigen processing. J Immunol. 1988 May 1;140(9):2893–2898. [PubMed] [Google Scholar]
- Manca F., Kunkl A., Fenoglio D., Fowler A., Sercarz E., Celada F. Constraints in T-B cooperation related to epitope topology on E. coli beta-galactosidase. I. The fine specificity of T cells dictates the fine specificity of antibodies directed to conformation-dependent determinants. Eur J Immunol. 1985 Apr;15(4):345–350. doi: 10.1002/eji.1830150408. [DOI] [PubMed] [Google Scholar]
- Michalek M. T., Benacerraf B., Rock K. L. Two genetically identical antigen-presenting cell clones display heterogeneity in antigen processing. Proc Natl Acad Sci U S A. 1989 May;86(9):3316–3320. doi: 10.1073/pnas.86.9.3316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ozaki S., Berzofsky J. A. Antibody conjugates mimic specific B cell presentation of antigen: relationship between T and B cell specificity. J Immunol. 1987 Jun 15;138(12):4133–4142. [PubMed] [Google Scholar]
- Scherle P. A., Gerhard W. Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin. J Exp Med. 1986 Oct 1;164(4):1114–1128. doi: 10.1084/jem.164.4.1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheshberadaran H., Payne L. G. Protein antigen-monoclonal antibody contact sites investigated by limited proteolysis of monoclonal antibody-bound antigen: protein "footprinting". Proc Natl Acad Sci U S A. 1988 Jan;85(1):1–5. doi: 10.1073/pnas.85.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
- Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]