Activated human epitope-specific T cells identified by class II tetramers reside within a CD4high, proliferating subset.
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 CD4(high) population is substantially enriched in epitope-specific cells identified by class II tetramer staining and almost all tetramer-positive cells are contained within the CD4(high) population. T cell clones derived from the tetramer-positive, CD4(high) population demonstrate antigen specificity and maintain tetramer staining, while the substantial number of CD4(high) 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.
Novak
E J
EJ
Virginia Mason Research Center, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101-2795, USA.
Masewicz
S A
SA
Liu
A W
AW
Lernmark
A
A
Kwok
W W
WW
Nepom
G T
GT
D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II