Simultaneous reconstitution of multiple cytomegalovirus-specific CD8+ cell populations with divergent functionality in hematopoietic stem-cell transplant recipients.
A panel of 7 human cytomegalovirus (CMV) epitope peptides and corresponding major histocompatibility class 1 tetramers was used to evaluate cellular immunity in healthy seropositive donors and in hematopoietic stem-cell transplant recipients. Broad CMV-specific T cell responses to epitopes were found within several CMV polypeptides and were restricted by multiple human leukocyte antigen alleles. Their cytotoxic functionality was evaluated by use of an assay that measures transient surface levels of lysosomal membrane proteins LAMP-1 (CD107a) and LAMP-2 (CD107b) after peptide stimulation. This assay can be combined with tetramer staining of antigen-specific CD8(+) T lymphocytes and has potential as a surrogate marker for cytotoxic function. CD8(+) T lymphocytes specific for epitopes within the pp65 or pp50 gene products exhibited significantly higher functionality, compared with populations recognizing CMV major immediate early-1 epitopes. These functional differences between T lymphocyte populations within the same individual may have implications for protection against CMV.
Lacey
Simon F
SF
Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, Duarte, California 91010-3000, USA. slacey@coh.org
Martinez
Joy
J
Gallez-Hawkins
Ghislaine
G
Thao
Lia
L
Longmate
Jeff
J
Haq
Wahajul
W
Spielberger
Ricardo
R
Forman
Stephen J
SJ
Zaia
John A
JA
Diamond
Don J
DJ
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D001782:Blood Donors; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015550:Cell Degranulation; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000276:immunology; D000939:Epitopes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015395:Histocompatibility Antigens Class I; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D010750:Phosphoproteins / Q000737:chemistry / Q000276:immunology; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000276:immunology
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D010455:Peptides; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D017361:Viral Nonstructural Proteins; C065418:cytomegalovirus matrix protein 65kDa; C087085:phosphoprotein 50, cytomegalovirus