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Generation of Immunity against Pathogens via Single-Domain Antibody–Antigen Constructs
- Source :
- The Journal of Immunology. 197:4838-4847
- Publication Year :
- 2016
- Publisher :
- The American Association of Immunologists, 2016.
-
Abstract
- mAbs specific for surface proteins on APCs can serve as Ag-delivery vehicles that enhance immunogenicity. The practical use of such constructs is limited by the challenge of expressing and modifying full-sized mAbs. We generated single-domain Ab fragments (VHHs) specific for class II MHC (MHCII), CD11b, and CD36. VHH sequences were modified by inclusion of a C-terminal sortase motif to allow site-specific conjugation with various Ag payloads. We tested T cell activation using VHHs that target distinct APC populations; anti-MHCII adducts elicited strong activation of CD4+ T cells, whereas anti-CD11b showed CD8+ T cell activation superior to targeting via MHCII and CD36. Differences in Ag presentation among constructs were unrelated to dendritic cell subtype or routing to acidic compartments. When coupled to antigenic payloads, anti-MHCII VHH primed Ab responses against GFP, ubiquitin, an OVA peptide, and the α-helix of influenza hemagglutinin’s stem; the last afforded protection against influenza infection. The versatility of the VHH scaffold and sortase-mediated covalent attachment of Ags suggests their broader application to generate desirable immune responses.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
T cell
Immunology
Antigen presentation
Hemagglutinin Glycoproteins, Influenza Virus
chemical and pharmacologic phenomena
Antigen-Antibody Complex
CD8-Positive T-Lymphocytes
Biology
Lymphocyte Activation
Major histocompatibility complex
Article
Mice
03 medical and health sciences
0302 clinical medicine
Orthomyxoviridae Infections
Antigen
Sortase
Influenza, Human
medicine
Animals
Humans
Immunology and Allergy
Cells, Cultured
Mice, Knockout
Antigen Presentation
Mice, Inbred BALB C
Immunogenicity
Histocompatibility Antigens Class II
Dendritic Cells
Dendritic cell
Single-Domain Antibodies
Molecular biology
Mice, Inbred C57BL
030104 developmental biology
Single-domain antibody
medicine.anatomical_structure
Influenza Vaccines
biology.protein
Camelids, New World
030215 immunology
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 197
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....2c5470a0504fac630dac58aab1650440