Relevance of peptide avidity to the T cell receptor for cytomegalovirus-specific ex vivo CD8 T cell cytotoxicity.
CD8(+) T cells contribute to the control of viral infection by several effector mechanisms, including lysis of virally infected cells and interferon (IFN)-gamma secretion. Ex vivo cytotoxicity and potent secretion of IFN-gamma in response to cytomegalovirus (CMV) epitope peptides was seen in freshly prepared unstimulated peripheral blood mononuclear cells from human immunodeficiency virus-infected patients with high T cell receptor (TCR)/peptide avidity. Lymphocytes with low TCR/peptide avidity had no ex vivo cytotoxicity, secreted minimal IFN-gamma, and could not recognize autologous infected targets. Despite this, ex vivo responding and nonresponding patients had substantial frequencies of tetramer-positive and IFN-gamma-secreting lymphocytes. Levels of activation and memory markers were also similar in tetramer-positive populations of both groups. However, cytolytic capacity remained in nonresponders; their lymphocytes regained cytotoxicity after in vitro stimulation with peptide without coactivators or interleukin-2. High-avidity CD8(+) T cells are likely important in viral control, and their generation should be a goal of therapeutic vaccination.
Villacres
Maria C
MC
Beckman Research Institute of the City of Hope, Duarte, USA.
Lacey
Simon F
SF
Auge
Catherine
C
Longmate
Jeff
J
Leedom
John M
JM
Diamond
Don J
DJ
D000915:Antibody Affinity; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D010446:Peptide Fragments; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C066890:T cell receptor-V(beta)8-39-59 peptide; D007371:Interferon-gamma