mAb against hen egg-white lysozyme regulate its presentation to CD4(+) T cells

Area of Science:

• Immunology
• Molecular Biology
• Protein Chemistry

Background:

• Antibodies enhance antigen uptake and presentation by antigen-presenting cells (APCs) through B cell receptors or Fcgamma receptors.
• The interaction between antibodies and antigens may modulate the repertoire of peptides presented by MHC class II molecules.

Purpose of the Study:

• To investigate how antibody-antigen interactions influence the presentation of specific T cell epitopes from hen egg-white lysozyme (HEL).
• To determine the role of antibody binding site, epitope accessibility, and antibody affinity in modulating MHC class II presentation.

Main Methods:

• Analysis of CD4(+) T cell epitope presentation of hen egg-white lysozyme (HEL) after immune complex formation with seven specific monoclonal antibodies (mAbs).
• Evaluation of T cell epitope presentation influenced by antibody binding site proximity, epitope accessibility (surface-exposed vs. buried), and antibody affinity.

Main Results:

• Specific mAbs binding to proximal loops of HEL selectively upregulated the I-E(d)-restricted 103-117 T cell epitope.
• mAbs overlapping surface-exposed, Ii-independent T cell epitopes (I-A(k)-restricted 116-129 and 34-45) upregulated their presentation, but higher affinity did not always enhance presentation.
• High-affinity mAbs targeting N- or C-terminal epitopes upregulated a buried, Ii-dependent T cell epitope (I-A(k)-restricted 45-61) requiring MHC class II resynthesis.

Conclusions:

• The spatial relationship between the T cell epitope and the B cell epitope recognized by the mAb is critical for modulating epitope presentation.
• Intrinsic processing requirements of T cell epitopes and antibody affinity significantly influence which epitopes are presented by MHC class II molecules.
• Antibody engineering can potentially control the presentation of specific T cell epitopes, impacting adaptive immune responses.