Use of antibody/peptide constructs of direct antigenic peptides to T cells: evidence for T cell processing and presentation.
Human T cells can express MHC-class II products and were shown to be potential antigen-presenting cells. However, they are unable to capture the antigen and only antigens, which bind to T cell membranes such as the gp120 glycoprotein of HIV, are internalized, processed, and presented by T cells. To better understand the role of T cells as antigen-presenting cells, we established a method which overcomes the lack of antigen capture by T cells. Antigen (tetanus toxoid, TT) or an antigenic peptide of TT (residue 830-843, P2) was coupled to antibodies directed to T cell surface molecules such as CD2, CD4, CD8. Antibody/TT and antibody/P2 constructs stimulated P2-specific T cell clones in the absence of accessory cells, if the antibody recognized a T cell surface structure. Compared to the peptide alone, a 100-500 times lower molar concentration of the antibody/peptide construct was required to achieve a similar proliferative response. T cell stimulation via the constructs involved intracellular processing, as nonspecific, glutaraldehyde fixed T cell lines pulsed with the constructs could present the peptide and processing inhibitors like Leupeptin or Chloroquine inhibited the development of a proliferative response to the constructs. Our data underline the ability of T cells to function as antigen-processing and -presenting cells and show that antibody/antigen or antibody/peptide constructs are able to direct a certain antigen or peptide to a T cell. Antibody/peptide constructs may be interesting tools to better understand antigen processing and to study the consequences of antigen presentation by different cells.
Wyss-Coray
T
T
Institute of Clinical Immunology, Inselspital, Bern, Switzerland.
Brander
C
C
Bettens
F
F
Mijic
D
D
Pichler
W J
WJ
D000936:Antigen-Antibody Complex / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000008:administration & dosage*; D002738:Chloroquine / Q000494:pharmacology; D002999:Clone Cells; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007976:Leupeptins / Q000494:pharmacology; D008213:Lymphocyte Activation; D010455:Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*
D000936:Antigen-Antibody Complex; D000942:Antigens, Bacterial; D007976:Leupeptins; D010455:Peptides; D013745:Tetanus Toxoid; D002738:Chloroquine; C032854:leupeptin