Recombinant antibodies for delivery of antigen: a single loop between beta-strands in the constant region can accommodate long, complex and tandem T cell epitopes.
Recombinant antibodies are increasingly used for efficient delivery of T cell epitopes to antigen-presenting cells (APCs), both for vaccination purposes and for immune modulation. We have previously shown that recombinant antibodies can accommodate single T cell epitopes inserted into loops between beta-strands in constant (C) domains. Such recombinant antibodies have in addition been equipped with variable regions that target APCs for increased delivery of C region T cell epitopes. We here show that loop 6 (loop FG) in C(H)1 of human gamma 3 can be exchanged with (i) long T cell epitopes up to 37 amino acids, (ii) epitopes with complex secondary structure such as gluten epitopes with a type II polyproline helical confirmation and (iii) two tandemly linked T cell epitopes. T cell responses increased with T cell epitope elongation, presumably due to a positive influence of flanking residues. Recombinant antibodies targeted to either CD14 on monocytes or HLA-DP on monocytes and dendritic cells gave similar results and were 2-4 logs more efficient at stimulating human T cells than were non-targeted controls. Thus, single loops in C regions of recombinant antibodies seem versatile and may be used for delivery of lengthy, complex and multiple T cell epitopes to human APCs.
Tunheim
Gro
G
Center for Immune Regulation, Institute of Immunology, Medical Faculty, University of Oslo and Rikshospitalet University Hospital, Norway.
Schjetne
Karoline W
KW
Rasmussen
Ingunn B
IB
Sollid
Ludvig M
LM
Sandlie
Inger
I
Bogen
Bjarne
B
D000906:Antibodies / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005983:Glutens / Q000276:immunology; D006682:HLA-DP Antigens / Q000276:immunology; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010455:Peptides / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
D000906:Antibodies; D000941:Antigens; D018984:Epitopes, T-Lymphocyte; C520137:FGLL peptide; D006682:HLA-DP Antigens; D007127:Immunoglobulin Constant Regions; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C011083:polyproline; D005983:Glutens