Activated human epitope-specific T cells identified by class II tetramers reside within a CD4(high), proliferating subset

Antigen-specific T cells acquire a distinctive phenotype during activation, with characteristic acquisition of surface markers and patterns of gene ex pression. Early after antigen stimulation, CD4(+) T lymphocytes increase th eir surface density of the CD4 marker, a trait which has been used to ident ify antigen-activated cells, The recent development of MHC tetramer technol ogies has greatly improved the ability to detect HLA class I-restricted T c ells specific for known antigen epitopes, We have recently extended these s tudies to human class II-restricted CD4(+) T cell responses and now describ e antigen-specific T cell responses from human peripheral blood in which el evated CD4 expression levels in human T cells following antigen stimulation identify the activated and proliferating subset of cells. The CD4(high) po pulation is substantially enriched in epitope-specific cells identified by class II tetramer staining and almost all tetramer-positive cells are conta ined within the CD4(high) population. T cell clones derived from the tetram er-positive, CD4(high) population demonstrate antigen specificity end maint ain tetramer staining, while the substantial number of CD4(high) cells whic h fail to stain with tetramer appear to proliferate as a result of bystande r activation. Epitope-specific components of a polyclonal immune response a re directly visualized and quantitated by tetramer detection, providing a d irect measure of the heterogeneity of the human immune response.