Nonclassical HLA-G molecules are classical peptide presenters

Diehl, Marianne; Münz, Christian; Keilholz, Wieland; Stevanović, Stefan; Holmes, N. C.; Loke, Y.W.; Rammensee, Hans‐Georg

doi:10.1016/s0960-9822(02)00481-5

Cited by 184 publications

(143 citation statements)

References 46 publications

Supporting

Mentioning

137

Contrasting

Order By: Relevance

“…The pp65-encoded peptides are designed based on the HLA-G-binding motif consensus sequence. Anchor residues are shown in bold, while underlined residues correspond to preferential residues listed from the peptides eluted from HLA-G (Lee et al, 1995;Diehl et al, 1996). Generation of peptide-specific CTLs.…”

Section: Methodsmentioning

confidence: 99%

“…The amino acid sequence of HCMV pp65 protein was screened for HLA-G-binding consensus anchor residues: proline at position 3 and leucine or isoleucine at position 9 (Diehl et al, 1996;Lee et al, 1995). Six peptides exhibiting the best position match were selected (Table 1) and then analysed for their capacity to stabilize HLA-G molecules on T2/G cells (DeMars et al, 1984).…”

Section: Identification Of Hla-g-binding Peptides Derived From Hcmv Pmentioning

confidence: 99%

“…HLA-G molecules have a peptide-binding groove that is homologous to those of classical MHC class I molecules. In addition, HLA-G was shown to present nonameric peptides derived from a variety of intracellular proteins (Diehl et al, 1996;Lee et al, 1995). It was proposed that HLA-G on trophoblast cells interacts with several inhibitory or triggering NK cell receptors to protect placental cells against the cytotoxic activity of NK cells (Lanier, 1999).…”

mentioning

confidence: 99%

“…The TAP1 2 /TAP2 2 -deficient T2 cell line (Salter & Cresswell, 1986) Peptide-binding assay. Six pp65-derived peptides were designed based on the HLA-G-binding motif (Diehl et al, 1996;Lee et al, 1995). We also used peptides eluted from HLA-G molecules (Lee et al, 1995) and an HLA-B27-binding peptide (Solache et al, 1999) as positive and negative controls, respectively.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Lenfant

Pizzato

Liang

et al. 2003

Journal of General Virology

View full text Add to dashboard Cite

The non-classical major histocompatibility complex class I molecule HLA-G is expressed mainly by extravillous trophoblasts at the materno-foetal interface. HLA-G has been found to bind endogenously processed nonameric peptides but its function as a restriction element for a cytotoxic T cell response to viruses with tropism for trophoblastic cells has never been demonstrated. In this study, candidate viral peptides derived from human cytomegalovirus (HCMV) pp65 (UL83), which stabilized the HLA-G molecule on HLA-G-transfected T2 cells, were identified. The specific antipp65 cytotoxic T lymphocyte (CTL) response restricted by HLA-G in triple transgenic mice (HLA-G, human b2m, human CD8a) was then investigated by injection of dendritic cells loaded with synthetic pp65-derived peptides or by infection with canarypox virus expressing pp65. Results showed that CTLs from HLA-G mice have the capacity to kill target cells either infected with recombinant vaccinia viruses expressing pp65 or loaded with specific pp65-derived peptides using HLA-G as an antigen-presenting molecule. It was also demonstrated that these HLA-G-restricted pp65-specific T cells are able to kill the human astrocytoma cell line U373, which was transfected with HLA-G and infected with HCMV. Moreover, using HLA-G tetramers refolded with a synthetic pp65-derived peptide, peptide-specific CD8 + cells restricted by HLA-G have been detected in vivo. These findings provide the first evidence that HLA-G can select anti-HCMV-restricted CTLs in vivo, although the potency of this cytolytic response is limited (20-25 %). The weak HLA-Grestricted anti-HCMV response is probably due to HLA-G-mediated inhibitory signals on the development of an antiviral CTL response. INTRODUCTIONDuring pregnancy, the placenta is the first barrier that protects the foetus from pathogens. It is of relevance, therefore, that trophoblast cells in placental tissues lack major histocompatibility (MHC) class I expression. These highly polymorphic MHC molecules, HLA-A and HLA-B, play a central role in the detection and elimination of infected cells by CD8 + T cells and natural killer (NK) cells. However, despite the general lack of classical MHC molecules, extravillous trophoblasts, a subpopulation of trophoblasts that is in direct contact with maternal cells, express low levels of HLA-C and at a higher extent, the non-classical HLA-Ib molecules HLA-G and HLA-E (Kovats et al., 1990;Le Bouteiller et al., 1999;King et al., 2000), which are accompanied by abundant expression of transporter-associated proteins (TAP) (Clover et al., 1995). The non-classical HLA-Ib molecule HLA-E binds preferentially to leader peptides of many MHC class I molecules (Braud et al., 1998;Lee et al., 1998) and these complexes function as ligands for CD94/NKG2 receptors on NK cells . HLA-G molecules have a peptide-binding groove that is homologous to those of classical MHC class I molecules. In addition, HLA-G was shown to present nonameric peptides derived from a variety of intracellular proteins (Diehl et al., 199...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Identification Of Hla-g-binding Peptides Derived From Hcmv Pmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Lenfant

Pizzato

Liang

et al. 2003

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…In contrast, the class Ib genes HLA-G, HLA-E and HLA-F display limited polymorphism (Robinson et al, 2003;Shawar et al, 1994). The peptide-binding repertoire of HLA-G is therefore restricted, with a defined peptide-binding motif (Ishitani et al, 2003;Diehl et al, 1996;Lee et al, 1995). Indeed, in the placenta a single peptide accounts for up to 15% of recovered ligand (Ishitani et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt

et al. 2005

View full text Add to dashboard Cite

HLA-G is a nonclassical class I major histocompatibility complex (MHC) molecule that is primarily expressed at the foetal-maternal interface. Although the role of HLA-G has not been fully elucidated, current evidence suggests it protects the foetus from the maternal immune response. In this report, HLA-G (44 kDa) is characterized by expression in Escherichia coli. The inclusion bodies were refolded in complex with a peptide derived from histone H2A (RIIPRHLQL), purified and subsequently crystallized. Correct refolding was determined using two conformation-dependent antibodies. Cobalt ions were shown to be an essential ingredient for obtaining diffraction-quality crystals. The crystals, which diffracted to 1.9 Å resolution, belonged to space group P3 2 2 1 , with unit-cell parameters a = b = 77.15, c = 151.72 Å .

show abstract

HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor

2002

View full text Add to dashboard Cite

Human histocompatibility leukocyte antigen (HLA)‐G is an MHC class Ib molecule that has been proposed to regulate immune responses during pregnancy. One of the possible mechanisms of that modulation is based on its interaction with immunoglobulin‐like transcript (ILT) receptors. In this study, we show that HLA‐G modifies the function of murine dendritic cells via interactions with the paired immunoglobulin‐like inhibitory receptor, a homologue of the human inhibitory receptor ILT4. Triggering of the immune inhibitory receptors resulted in prolongation of allogeneic graft survival. This demonstration forms the basis for exploring and exploiting HLA‐G molecules and immune inhibitory receptors in the development of a new therapeutic strategy to improve allogeneic graft survival.

show abstract

Nonclassical HLA-G molecules are classical peptide presenters

Cited by 184 publications

References 46 publications

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice

The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt

HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor

Contact Info

Product

Resources

About