MHC class II‐associated invariant chain peptide replacement by T cell epitopes: engineered invariant chain as a vehicle for directed and enhanced MHC class II antigen processing and presentation

• Published in: European journal of immunology 1998-05, Vol.28 (5), p.1524-1533
• Main Authors: Malcherek, Georg, Wirblich, Christoph, Willcox, Nicholas, Rammensee, Hans‐Georg, Trowsdale, John, Melms, Arthur
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antigen presentation; Antigen Presentation - genetics; Antigens, Differentiation, B-Lymphocyte - genetics; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Differentiation, B-Lymphocyte - metabolism; Class II‐associated invariant chain peptide; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Genetic Vectors - chemical synthesis; Genetic Vectors - immunology; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; HLA-DR4 Antigen - metabolism; Humans; Intracellular Fluid - metabolism; Invariant chain hybrid; Lymphocyte Activation; Molecular Sequence Data; Protein Binding - genetics; Protein Engineering; Receptors, Cholinergic - genetics; Receptors, Cholinergic - immunology; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; T cell epitope; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tetanus Toxin - genetics; Tetanus Toxin - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199805)28:05<1524::AID-IMMU1524>3.0.CO;2-T

Proteolysis of the invariant chain (Ii) leads to the generation of abundant MHC class II‐associated invariant chain peptides (CLIP), which bind in the MHC class II binding groove via supermotifs in a manner similar to that of antigenic peptides. We have engineered an Ii vector with the capacity to express any antigenic peptide of interest instead of CLIP, for T cell stimulation. When peripheral blood mononuclear cells (PBMC) were pulsed with Ii hybrids encoding T cell epitopes of tetanus toxin or acetylcholine receptor, stimulation of T cells was dramatically enhanced compared to stimulation after priming with either the native or recombinant proteins. Site‐specific insertion of antigenic sequences into the CLIP region promoted enhanced antigenicity of Ii hybrids which were shown to be processed intracellularly in a chloroquine‐sensitive compartment. Naturally processed T helper epitopes were visualized directly on the surface of PBMC and identified as analogs of CLIP associated with MHC class II molecules. This novel Ii vector provides a flexible and efficient system for the delivery of defined peptide epitopes to T cells which might be useful in the development of specific vaccines and in the study of intracellular processing.