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. 1994 Jan;81(1):167–170.

Antigen targeting to antigen-presenting cells enhances presentation to class II-restricted T lymphocytes.

A Scardino 1, M Paroli 1, G De Petrillo 1, M L Michel 1, V Barnaba 1
PMCID: PMC1422286  PMID: 7907575

Abstract

Receptor-mediated uptake increases by several orders of magnitude the efficiency of APC to internalize Ag, and is stringently required for the Ag-presenting function of T lymphocytes due to their inability to take up Ag non-specifically. We have previously reported that hepatitis B envelope antigen (HBenvAg) can be internalized by T cells via transferrin receptor (TfR). To evaluate if Ag targeting to receptors expressed on APC could be an effective tool for promoting Ag uptake and presentation, we tested the capacity of activated T cells not expressing TfR to induce HBenvAg-specific T-cell responses when pulsed with a hybrid particle containing HBenvAg coupled to gp120 of human immunodeficiency virus (HIV), exploiting the ability of gp120 to bind to CD4 receptor. We found that CD4+/TfR- T cells pulsed either with the hybrid particle or peptide (S193-207) but not with S, L Ag, a recombinant form of HBenvAg, induced a specific proliferative response of a T-cell clone recognizing peptide (S193-207) of HBenvAg. The finding that the addition of anti-CD4 monoclonal antibody (mAb) before the pulsing of CD4+/TfR- T cells with the hybrid particle drastically blocked the specific T-cell response, together with the finding that CD8+/TfR- T cells were unable to serve as APC even if pulsed with this molecule, demonstrated that CD4 receptor was crucial for the HBenvAg internalization. On the other hand, HBenvAg presentation by CD4+/TfR+ T cells pulsed with the hybrid particle was inhibited only when both anti-CD4 and anti-TfR were added before the pulsing. These results suggest that Ag targeting to APC receptors may be usefully exploited to improve Ag-presentation efficiency in potential immunotherapeutic approaches.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Azuma M., Yssel H., Phillips J. H., Spits H., Lanier L. L. Functional expression of B7/BB1 on activated T lymphocytes. J Exp Med. 1993 Mar 1;177(3):845–850. doi: 10.1084/jem.177.3.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnaba V., Franco A., Alberti A., Benvenuto R., Balsano F. Selective killing of hepatitis B envelope antigen-specific B cells by class I-restricted, exogenous antigen-specific T lymphocytes. Nature. 1990 May 17;345(6272):258–260. doi: 10.1038/345258a0. [DOI] [PubMed] [Google Scholar]
  3. Franco A., Paroli M., Testa U., Benvenuto R., Peschle C., Balsano F., Barnaba V. Transferrin receptor mediates uptake and presentation of hepatitis B envelope antigen by T lymphocytes. J Exp Med. 1992 May 1;175(5):1195–1205. doi: 10.1084/jem.175.5.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ko H. S., Fu S. M., Winchester R. J., Yu D. T., Kunkel H. G. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med. 1979 Aug 1;150(2):246–255. doi: 10.1084/jem.150.2.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. LaSalle J. M., Ota K., Hafler D. A. Presentation of autoantigen by human T cells. J Immunol. 1991 Aug 1;147(3):774–780. [PubMed] [Google Scholar]
  6. Lanzavecchia A., Abrignani S., Scheidegger D., Obrist R., Dörken B., Moldenhauer G. Antibodies as antigens. The use of mouse monoclonal antibodies to focus human T cells against selected targets. J Exp Med. 1988 Feb 1;167(2):345–352. doi: 10.1084/jem.167.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lanzavecchia A. Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes. Annu Rev Immunol. 1990;8:773–793. doi: 10.1146/annurev.iy.08.040190.004013. [DOI] [PubMed] [Google Scholar]
  8. Lanzavecchia A., Roosnek E., Gregory T., Berman P., Abrignani S. T cells can present antigens such as HIV gp120 targeted to their own surface molecules. Nature. 1988 Aug 11;334(6182):530–532. doi: 10.1038/334530a0. [DOI] [PubMed] [Google Scholar]
  9. Lorenz R. G., Blum J. S., Allen P. M. Constitutive competition by self proteins for antigen presentation can be overcome by receptor-enhanced uptake. J Immunol. 1990 Mar 1;144(5):1600–1606. [PubMed] [Google Scholar]
  10. McCoy K. L., Noone M., Inman J. K., Stutzman R. Exogenous antigens internalized through transferrin receptors activate CD4+ T cells. J Immunol. 1993 Mar 1;150(5):1691–1704. [PubMed] [Google Scholar]
  11. Michel M. L., Mancini M., Sobczak E., Favier V., Guetard D., Bahraoui E. M., Tiollais P. Induction of anti-human immunodeficiency virus (HIV) neutralizing antibodies in rabbits immunized with recombinant HIV--hepatitis B surface antigen particles. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7957–7961. doi: 10.1073/pnas.85.21.7957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sansom D. M., Hall N. D. B7/BB1, the ligand for CD28, is expressed on repeatedly activated human T cells in vitro. Eur J Immunol. 1993 Jan;23(1):295–298. doi: 10.1002/eji.1830230148. [DOI] [PubMed] [Google Scholar]
  13. Schlienger K., Mancini M., Rivière Y., Dormont D., Tiollais P., Michel M. L. Human immunodeficiency virus type 1 major neutralizing determinant exposed on hepatitis B surface antigen particles is highly immunogenic in primates. J Virol. 1992 Apr;66(4):2570–2576. doi: 10.1128/jvi.66.4.2570-2576.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Siliciano R. F., Lawton T., Knall C., Karr R. W., Berman P., Gregory T., Reinherz E. L. Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion. Cell. 1988 Aug 12;54(4):561–575. doi: 10.1016/0092-8674(88)90078-5. [DOI] [PubMed] [Google Scholar]
  15. 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]

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