Epitopes described in "Long-term persistence of CD4(+) but rapid disappearance of CD8(+) T cells expressing an MHC class I-restricted TCR of nanomolar affinity."

Article Authors:Boris Engels; Adam S Chervin; Andrea J Sant; David M Kranz; Hans Schreiber
Article Title:Long-term persistence of CD4(+) but rapid disappearance of CD8(+) T cells expressing an MHC class I-restricted TCR of nanomolar affinity.
Reference Detail
Reference ID:1022872
Abstract:Most T cells have T cell receptors (TCR) of micromolar affinity for peptide-major histocompatibility complex (MHC) ligands, but genetic engineering can generate TCRs of nanomolar affinity. The affinity of the TCR used, m33, for its cognate non-self peptide-MHC-I complex (SIYRYYGL-K(b)) is 1,000-fold higher than of the wild-type TCR 2C. The affinity of m33 for the self-peptide dEV-8 on K(b) is only twofold higher. Mouse CD8(+) T cells transduced with an m33-encoding retrovirus showed binding of SIY-K(b) and potent function in vitro, but in vivo these T cells disappeared within hours after transfer into syngeneic hosts without causing graft-versus-host disease (GVHD). Accordingly, in cases where such CD8-dependent self-reactivity might occur in human adoptive T cell therapies, our results show that a peripheral T-cell deletion mechanism could operate to avoid reactions with the host. In contrast to CD8(+) T cells, we show that CD4(+) T cells expressing m33 survived for months in vivo. Furthermore, the m33-transduced CD4(+) T cells were able to mediate antigen-specific rejection of 6-day-old tumors. Together, we show that CD8(+) T cell expressing a MHC class I-restricted high-affinity TCR were rapidly deleted whereas CD4(+) T cells expressing the same TCR survived and provided function while being directed against a class I-restricted antigen.
Affiliations:Department of Pathology, Committee on Immunology, The University of Chicago, Chicago, Illinois 60637-5420, USA. bengels@bsd.uchicago.edu.
Reference Type:Literature
PubMed ID:22233579
Journal:Mol Ther
Journal Volume:20
Article Pages:652-60
Journal ISSN:1525-0024
Article Chemical List:Histocompatibility Antigens Class I;Oligopeptides;Peptides;Receptors, Antigen, T-Cell;superagonist SIYR
Article MeSH List:Amino Acid Sequence; Animals; CD4-Positive T-Lymphocytes(immunology; metabolism); CD8-Positive T-Lymphocytes(immunology; metabolism); Cell Line; Cell Survival(immunology); Gene Expression; Genetic Vectors(genetics); Histocompatibility Antigens Class I(immunology); Immunotherapy, Adoptive; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Neoplasms(genetics; immunology; therapy); Oligopeptides(immunology); Peptides(chemistry; immunology); Receptors, Antigen, T-Cell(genetics; immunology); Retroviridae(genetics); Transduction, Genetic
Curation Last Updated:2015-07-30 20:45:02