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

Int Immunol. 2008 Mar;20(3):295-306. doi: 10.1093/intimm/dxm141. Epub 2008 Feb 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / chemistry
  • Antibodies / genetics
  • Antibodies / immunology*
  • Antibody Specificity
  • Antigen Presentation
  • Antigens / administration & dosage*
  • Epitopes, T-Lymphocyte / immunology*
  • Glutens / immunology
  • HLA-DP Antigens / immunology
  • Humans
  • Immunoglobulin Constant Regions / immunology*
  • Leukocytes, Mononuclear / immunology
  • Peptides / immunology
  • Protein Transport / immunology
  • Recombinant Fusion Proteins / immunology*
  • Vaccines / immunology

Substances

  • Antibodies
  • Antigens
  • Epitopes, T-Lymphocyte
  • FGLL peptide
  • HLA-DP Antigens
  • Immunoglobulin Constant Regions
  • Peptides
  • Recombinant Fusion Proteins
  • Vaccines
  • polyproline
  • Glutens