Modulation of antigen processing by bound antibodies can boost or suppress class II major histocompatibility complex presentation of different T cell determinants.

• DOI: 10.1084/jem.181.6.1957
• Publication Date: 2004-06-24T07:56:10Z
• Authors: P D Simitsek; D G Campbell; A Lanzavecchia; N Fairweather; C Watts
• Keywords: 0301 basic medicine; Transcription, Genetic; Protein Conformation; T-Lymphocytes; Molecular Sequence Data; 610; Lymphocyte Activation; Chromatography, Affinity; Epitopes; Immunoglobulin Fab Fragments; 03 medical and health sciences; Tetanus Toxin; /dk/atira/pure/subjectarea/asjc/2700/2723; Humans; name=Immunology; Amino Acid Sequence; /dk/atira/pure/subjectarea/asjc/2400/2403; B-Lymphocytes; HLA-D Antigens; Antibodies, Monoclonal; Peptide Fragments; Clone Cells; name=Immunology and Allergy; Models, Structural; Kinetics; Protein Biosynthesis

Bound antibodies can modulate antigen processing but it is not clear to what extent this affects antigen presentation. Here we show that presentation of T cell determinants in tetanus toxin can be either enhanced or suppressed as a direct consequence of antibody modulation of antigen processing in human B lymphoblastoid cells. Remarkably, a single bound antibody or its Fab fragment can simultaneously enhance the presentation of one T cell determinant by more than 10-fold while strongly suppressing the presentation of a different T cell determinant. Biochemical analysis demonstrates that both the suppressed and boosted determinants fall within an extended domain of antigen stabilized or "footprinted" by this antibody during proteolysis. These results demonstrate that bound antibodies can modulate the capture of peptides by class II major histocompatibility complex (MHC), thus manipulating the T cell response towards or away from particular determinants. Altered processing of protein-protein complexes leading to enhanced loading of class II MHC and substantially lowered threshold for T cell activation suggests a novel mechanism that might reveal "cryptic" self determinants.