Soluble HLA/peptide monomers cross-linked with co-stimulatory antibodies onto a streptavidin core molecule efficiently stimulate antigen-specific T cell responses.
Soluble MHC-peptide complexes, commonly referred to as tetramers, have been shown to induce strong cross-linking of TCR and CD8, resulting in a vigorous activation followed by a rapid non-apoptotic CD8(+) T cell death. This has limited tetramer use for antigen-specific T cells isolation and cloning, as sorted tetramer positive cells were shown to possess compromised functional integrity. Here we show that the cross-linking of a secondary co-stimulatory signal into oligomeric MHC:peptide complexes prevents such cell death, and in contrast strongly stimulates antigen-specific T cell responses. Such soluble antigen-presenting complexes (sAPCs) containing MHC:peptide complexes linked to either anti-CD27 or anti-CD28 antibodies were capable of priming and expanding HLA-A*0201 restricted CMV specific T cells and also of generating functional HLA-A*0301 restricted BCR/ABL-specific T cell responses. These sAPCs constitute an encouraging alternative method for generating antigen-specific T cells that could be applied to a variety of antigens.
Anthony Nolan Research Institute, The Royal Free Hospital, University College of London, Hampstead, London NW3 2QG, UK.
Sylvie
S
Rusakiewicz
Geraldine
G
Aubert
Richard E
RE
Clark
Alejandro J
AJ
Madrigal
Anthony I
AI
Dodi
Paul J
PJ
Travers
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000276:immunology / Q000378:metabolism; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D019809:Streptavidin / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; C442141:HLA-A*03:01 antigen; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D010446:Peptide Fragments; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019809:Streptavidin; D016044:Fusion Proteins, bcr-abl