ANTIGEN TARGETING TO ANTIGEN-PRESENTING CELLS ENHANCES PRESENTATION TO CLASS II-RESTRICTED T-LYMPHOCYTES

Receptor-mediated uptake increases by several orders of magnitude the efficiency of APC to internalize Ag, and is stringently required for t he Ag-presenting function of T lymphocytes due to their inability to t ake up Ag non-specifically. We have previously reported that hepatitis B envelope antigen (HBenvAg) can be internalized by T cells via trans ferrin receptor (TfR). To evaluate if Ag targeting to receptors expres sed on APC could be an effective tool for promoting Ag uptake and pres entation, we tested the capacity of activated T cells not expressing T fR to induce HBenvAg-specific T-cell responses when pulsed with a hybr id particle containing HBenvAg coupled to gp120 of human immunodeficie ncy virus (HIV), exploiting the ability of gp120 to bind to CD4 recept or. We found that CD4(+)/TfR(-) T cells pulsed either with the hybrid particle or peptide (S-193-207) but not with S,L Ag, a recombinant for m of HBenvAg, induced a specific proliferative response of a T-cell cl one recognizing peptide (S-193-207) Of HBenvAg. The finding that the a ddition of anti-CD4 monoclonal antibody (mAb) before the pulsing of CD 4(+)/TfR(-) T cells with the hybrid particle drastically blocked the s pecific 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 internaliz ation. On the other hand, HBenvAg presentation by CD4(+)/TfR(+) T cell s pulsed with the hybrid particle was inhibited only when both anti-CD 4 and anti-TfR were added before the pulsing. These results suggest th at Ag targeting to APC receptors may be usefully exploited to improve Ag-presentation efficiency in potential immunotherapeutic approaches.