Peptide length extension skews the minor HA-1 antigen presentation toward activated dendritic cells but reduces its presentation efficiency.
J Immunol
; 185(8): 4582-9, 2010 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-20855877
ABSTRACT
Minor histocompatibility Ags (mHags) are important targets of the graft-versus-leukemia effect after HLA-matched allogeneic stem cell transplantation. mHags are HLA-restricted polymorphic peptides expressed on normal and leukemia cells. Vaccination with hematopoiesis-restricted mHag peptides, such as HA-1, may boost the graft-versus-leukemia effect. However, some animal studies indicate that peptides exactly reflecting immunogenic T cell epitopes (short peptides [SPs]) induce tolerance that is potentially due to systemic Ag spreading. Peptide length extension (long peptides [LPs]) may optimize immune responses by restricting and prolonging Ag presentation on dendritic cells (DCs). In this study, we compared the in vitro characteristics and T cell-stimulatory capacities of a human 30-mer HA-1 LP with the 9-mer HA-1 SP. DCs presented the HA-1 LP and SP and expanded HA-1-specific cytotoxic T cell lines. As hypothesized, HA-1 LP presentation, but not SP presentation, was largely restricted to activated DCs and was nearly absent on other hematopoietic cells. However, DCs presented the HA-1 LP 2-3 log levels less efficiently than the SP. Finally, the decay of HA-1 LP and SP presentation on DCs was comparable. We conclude that HA-1 LP and SP differ in their in vitro characteristics and that only comparative clinical studies after allogeneic stem cell transplantation may reveal the optimal HA-1 vaccine.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Células Dendríticas
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Ativação Linfocitária
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Linfócitos T Citotóxicos
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Antígenos de Histocompatibilidade Menor
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Apresentação de Antígeno
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article