International Immunology, Vol. 13, No. 6, 799-806,
June 2001
© 2001 Japanese Society for Immunology
Activated human epitope-specific T cells identified by class II tetramers reside within a CD4high, proliferating subset
1 Virginia Mason Research Center, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101-2795, USA
2 R. H. Williams Laboratory, Molecular and Cellular Biology Program and Department of Medicine, University of Washington, Seattle, WA 98195, USA
Correspondence to: G. T. Nepom
Antigen-specific T cells acquire a distinctive phenotype during activation, with characteristic acquisition of surface markers and patterns of gene expression. Early after antigen stimulation, CD4+ T lymphocytes increase their surface density of the CD4 marker, a trait which has been used to identify antigen-activated cells. The recent development of MHC tetramer technologies has greatly improved the ability to detect HLA class I-restricted T cells specific for known antigen epitopes. We have recently extended these studies to human class II-restricted CD4+ T cell responses and now describe antigen-specific T cell responses from human peripheral blood in which elevated CD4 expression levels in human T cells following antigen stimulation identify the activated and proliferating subset of cells. The CD4high population is substantially enriched in epitope-specific cells identified by class II tetramer staining and almost all tetramer-positive cells are contained within the CD4high population. T cell clones derived from the tetramer-positive, CD4high population demonstrate antigen specificity and maintain tetramer staining, while the substantial number of CD4high cells which fail to stain with tetramer appear to proliferate as a result of bystander activation. Epitope-specific components of a polyclonal immune response are directly visualized and quantitated by tetramer detection, providing a direct measure of the heterogeneity of the human immune response.
Keywords: cellular activation, FACS, HLA, MHC, T Lymphocytes
Transmitting editor: A. McMichael
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