Human CD8(+) T cell responses against five newly identified respiratory syncytial virus-derived epitopes.
CD8(+) T lymphocytes play a major role in the clearance of respiratory syncytial virus (RSV) infections. To be able to study the primary CTL response in RSV-infected children, epitopes presented by a set of commonly used HLA alleles (HLA-A1, -A3, -B44 and -B51) were searched for. Five epitopes were characterized derived from the matrix (M), non-structural (NS2) and second matrix (M2) proteins of RSV. All epitopes were shown to be processed and presented by RSV-infected antigen-presenting cells. HLA-A1 tetramers for one of these epitopes derived from the M protein were constructed and used to quantify and phenotype the memory CD8(+) T cell pool in a panel of healthy adult donors. In about 60 % of the donors, CD8(+) T cells specific for the M protein could be identified. These cells belonged to the memory T cell subset characterized by expression of CD27 and CD28, and down-regulation of CCR7 and CD45RA. The frequency of tetramer-positive cells varied between 0.4 and 3 per 10(4) CD8(+) T cells in PBMC of healthy asymptomatic adult donors.
Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center, KE 04.133.1, PO Box 85500, 3508 AB Utrecht, The Netherlands.
Jojanneke
J
Heidema
Division of Pulmonology and the Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
Godelieve J
GJ
de Bree
Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center, KE 04.133.1, PO Box 85500, 3508 AB Utrecht, The Netherlands.
Patricia M A
PMA
de Graaff
Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center, KE 04.133.1, PO Box 85500, 3508 AB Utrecht, The Netherlands.
Wendy W C
WWC
van Maren
The Netherlands Vaccine Institute, Bilthoven, The Netherlands.
Peter
P
Hoogerhout
Division of Clinical Immunology, Academic Medical Center, Amsterdam, The Netherlands.
Theo A
TA
Out
Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center, KE 04.133.1, PO Box 85500, 3508 AB Utrecht, The Netherlands.
Jan L L
JLL
Kimpen
Division of Pediatrics, Wilhelmina Children's Hospital, University Medical Center, KE 04.133.1, PO Box 85500, 3508 AB Utrecht, The Netherlands.
Grada M
GM
van Bleek
D000328:Adult; D000483:Alleles; D001665:Binding Sites; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens / Q000235:genetics / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000502:physiology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*
C515370:CCR7 protein, human; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D054400:Receptors, CCR7; D019707:Receptors, Chemokine