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- Title
Soluble HLA/peptide monomers cross-linked with co-stimulatory antibodies onto a streptavidin core molecule efficiently stimulate antigen-specific T cell responses.
- Authors
Rusakiewicz, Sylvie; Aubert, Geraldine; Clark, Richard E.; Madrigal, Alejandro J.; Dodi, Anthony I.; Travers, Paul J.
- Abstract
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.
- Subjects
HLA histocompatibility antigens; IMMUNOGLOBULINS; STREPTAVIDIN; T cells; CELL death; TETRAMERS (Oligomers); LYMPHOCYTES; MEDICAL care
- Publication
Cancer Immunology, Immunotherapy, 2009, Vol 58, Issue 9, p1459
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-009-0711-x