Targeting to porcine sialoadhesin receptor improves antigen presentation to T cells.
Antibody-mediated targeting of antigen to specific antigen presenting cells (APC) receptors is an attractive strategy to enhance T cell immune responses to weak immunogenic antigens. Here, we describe the characterization of two monoclonal antibodies (mAb) against different epitopes of porcine sialoadhesin (Sn) and evaluate in vitro the potential of targeting this receptor for delivery of antigens to APC for T cell stimulation. The specificity of these mAb was determined by amino acid sequence analysis of peptides derived from the affinity purified antigen. Porcine Sn is expressed by macrophages present in the border between white and red pulp of the spleen and in the subcapsular sinus of lymph nodes, an appropriate location for trapping blood and lymph-borne antigens. It is also expressed by alveolar macrophages and monocyte-derived dendritic cells (MoDC). Blood monocytes are negative for this molecule, but its expression can be induced by treatment with IFN-alpha. MAb bound to Sn is rapidly endocytosed. MAb to sialoadhesin induced in vitro T cell proliferation at concentrations 100-fold lower than the non-targeting control mAb when using T lymphocytes from pigs immunized with mouse immunoglobulins as responder cells and IFN-alpha treated monocytes or MoDC as APC, suggesting a role of sialoadhesin in antigen uptake and/or delivery into the presentation pathway in APC.
Revilla
Concepción
C
Dpto. Biotecnología, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040, Madrid, Spain. crevilla@inia.es
Poderoso
Teresa
T
Martínez
Paloma
P
Alvarez
Belén
B
López-Fuertes
Laura
L
Alonso
Fernando
F
Ezquerra
Angel
A
Domínguez
Javier
J
D000818:Animals; D000911:Antibodies, Monoclonal; D017951:Antigen Presentation; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003713:Dendritic Cells / Q000502:physiology; D007136:Immunoglobulins / Q000276:immunology; D016898:Interferon-alpha; D008198:Lymph Nodes; D008264:Macrophages; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D011971:Receptors, Immunologic / Q000378:metabolism*; D063267:Sialic Acid Binding Ig-like Lectin 1; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013552:Swine / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse