Human herpesvirus 6 downregulates major histocompatibility complex class I in dendritic cells

2001 ◽  
Vol 65 (3) ◽  
pp. 576-583 ◽  
Author(s):  
Yuko Hirata ◽  
Kazuhiro Kondo ◽  
Koichi Yamanishi
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Human Herpesvirus ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Human Herpesvirus 6 ◽  
Histocompatibility Complex ◽  
Herpesvirus 6

scholarly journals A Human Herpesvirus 7 Glycoprotein, U21, Diverts Major Histocompatibility Complex Class I Molecules to Lysosomes

2001 ◽  
Vol 75 (24) ◽  
pp. 12347-12358 ◽  
Author(s):  
Amy W. Hudson ◽  
Peter M. Howley ◽  
Hidde L. Ploegh
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cytotoxic T Lymphocytes ◽  
Human Herpesvirus ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Immune Detection

ABSTRACT All members of the herpesvirus family persist in their host throughout life. In doing so, herpesviruses exploit a surprising number of different strategies to evade the immune system. Human herpesvirus 7 (HHV-7) is a relatively recently discovered member of the herpesvirus family, and little is known about how it escapes immune detection. Here we show that HHV-7 infection results in premature degradation of major histocompatibility complex class I molecules. We identify and characterize a protein from HHV-7, U21, that binds to and diverts properly folded class I molecules to a lysosomal compartment. Thus, U21 is likely to function in the normal course of HHV-7 infection to downregulate surface class I molecules and prevent recognition of infected cells by cytotoxic T lymphocytes.

scholarly journals Treatment of a glioblastoma patient by vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I–matched tumor peptides

2000 ◽  
Vol 9 (6) ◽  
pp. 1-5 ◽  
Author(s):  
Linda M. Liau ◽  
Keith L. Black ◽  
Neil A. Martin ◽  
Steven N. Sykes ◽  
Jeff M. Bronstein ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Immune Responses ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Outpatient Basis ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Dendritic cells (DCs) are antigen-presenting cells that play a central role in the initiation and modulation of antitumor immune responses. In this pilot study, we investigated the ability of autologous DCs pulsed ex vivo with allogeneic major histocompatibility complex class I–matched glioblastoma peptides to stimulate host antitumor immune responses when injected as a vaccine. A patient with recurrent brainstem glioblastoma multiforme (GBM) received a series of three intradermal immunizations of antigen-pulsed DCs on an outpatient basis following surgical debulking of her posterior fossa tumor. Dendritic cell vaccination was well tolerated, and no clinical signs of autoimmunity or experimental allergic en-cephalomyelitis were detected. She developed a measurable cellular immune response against the allogeneic glioblastoma peptides used in her vaccine preparation, as demonstrated by in vitro T-cell proliferation assays. In addition, increased T-cell infiltration was noted within the intracranial tumor site in the biopsy sample obtained following DC vaccination. An objective clinical response, however, was not evident, and this patient eventually died 21 months after her disease was diagnosed. To our knowledge, this is the first patient with brain cancer ever to be treated with DC-based immunotherapy. This case illustrates that vaccination with DCs pulsed with acid-eluted glioblastoma peptides is feasible and can induce systemic antigen-specific immunity in a patient with recurrent GBM. Additional studies are necessary to determine the optimum DC doses and antigen loading conditions that may translate into clinical effectiveness and survival benefit for patients with brain tumors. Phase I trials for malignant glioma are currently underway.

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