title: Two intermediate-avidity cytotoxic T lymphocyte clones with a disparity between functional avidity and MHC tetramer staining.
abstract: The efficacy of cytotoxic T lymphocytes (CTL) has been shown to be highly dependent upon their functional avidity (the sensitivity of their cellular response to MHC-peptide complexes). To examine this relationship, we employed target cell lysis as a quantitative measure and established a set of four CTL clones that exhibited a range of functional avidities spanning more than three orders of magnitude. Within this set, clones displayed a linear correlation between functional avidity and the TCR down-regulation that occurred in response to increasing antigen density. Staining intensity of MHC-peptide tetramer, however, correlated only with the very highest and very lowest avidity clones; the two intermediate-avidity clones showed an inverse relationship between tetramer staining and functional avidity. Compensation for differences in surface levels of TCR improved the correlation, but failed to fully account for this discrepancy. Comparison of TCR signals generated by stimulation of CTL with substrate-bound soluble MHC-peptide or antigen-presenting cells suggested that internal TCR signaling efficiency accounts for at least a portion of the observed functional avidity and suggests the need for caution in directly relating tetramer staining to avidity.
authors.affiliation: Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Derby
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: D H
authors.initials: DH
authors.lastname: Margulies
authors.forename: J A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000032:analysis* / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D013194:Staining and Labeling; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D016827:CD8 Antigens; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta