Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.
Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation.
Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA, USA.
Elizabeth
E
Townsley
Marcia
M
Woda
Stephen J
SJ
Thomas
Siripen
S
Kalayanarooj
Robert V
RV
Gibbons
Ananda
A
Nisalak
Anon
A
Srikiatkhachorn
Sharone
S
Green
Henry A F
HA
Stephens
Alan L
AL
Rothman
Anuja
A
Mathew
D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation; D008297:Male; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins
CD71; CD8+ T cells; HLA-B57; dengue; transferrin