Distinctive Features of the α1-Domain a Helix of HLA-C Heavy Chains Free of β2-Microglobulin

Setini, Andrea; Beretta, Alberto; Santis, Claudio De; Meneveri, Raffaella; Martayan, Aline; Mazzilli, Maria Cristina; Appella, Ettore; Siccardi, Antonio G.; Natali, Pier Giorgio; Giacomini, Patrizio

doi:10.1016/0198-8859(96)00011-0

Cited by 61 publications

(91 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VSV-G env and the HIV-1 env and rev sequences of the HIV-1 subtype B strains QH0692.42, AC10, 6535.5 and pRHPA4259.7 and subtype D strain NDK were obtained through the MRC CFAR NIBSC programme. mAbs L31 (Grassi et al, 1991;Setini et al, 1996) and W6/32 (Natali et al, 1989) were provided by Dr P. Giacomini (Laboratory of Immunology, Regina Elena Cancer Institute CRS, Rome, Italy). mAb M01 16/4/1 (anti-p24) was donated from Polymun, Germany.…”

Section: Discussionmentioning

confidence: 99%

“…FACS analysis (Fig. 2b) showed an almost complete downregulation of HLA-C [measured using mAb L31 (Grassi et al, 1991;Setini et al, 1996), which is specific for HLA-C open conformers]. The bulk of MHC class I, measured by mAb W6/32 (Natali et al, 1989), specific for all trimericconformation class I molecules, showed a reduction compatible with the silencing of HLA-C and the conservation of HLA-A and -B, as already seen by RNA analysis.…”

Section: Hla-c Sirna Silencing In Cell Linesmentioning

confidence: 99%

“…Therefore, infected cells display reduced detection by both cytotoxic lymphocytes and natural killer (NK) cells (Cohen et al, 1999). The hypothesis that HLA-C might exert an effect directly on HIV infectivity was originally suggested by De Santis et al (1996), exploiting the peculiar specificity of monoclonal antibody (mAb) L31 to show that normal levels of Env-driven fusion were restored in HLA-C transfectants (Grassi et al, 1991;Setini et al, 1996) of an MHC-deleted (fusion-incompetent) cell line. The physiological relevance of this finding is confirmed in this report, where small interfering RNA (siRNA) technology was used to silence HLA-C expression in peripheral blood lymphocytes (PBLs), the natural target of HIV-1.…”

Section: Introductionmentioning

confidence: 99%

“…FACS analysis (Fig. 2b) showed an almost complete downregulation of HLA-C [measured using mAb L31 (Grassi et al, 1991;Setini et al, 1996) virus (VSV-G)] on HLA-C-silenced target cells was measured using TZM-bl cells in a single-cycle assay. The efficiency of HIV pseudovirus infection (measured by Tatdriven luciferase production) was significantly reduced in HLA-C-silenced cells (NDK, P50.0028; QH0692.42, P50.002; pRHPA4259.7, P,0.0001; Fig.…”

mentioning

confidence: 99%

“…virion as well as cellular components. The relationship between the two HLA-C effects (on virus infectivity and target cell infectability) remains unclear.The specificity of mAb L31 (Grassi et al, 1991) has been documented extensively (Setini et al, 1996): L31 binds the KYK a1 motif, characteristic of all HLA-C alleles and accessible only on open conformers (i.e. molecules devoid of peptide with or without b 2 -microglobulin).…”

mentioning

confidence: 99%

See 4 more Smart Citations

HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

Baroni

Matucci

Scarlatti

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

The hypothesis that open conformers of HLA-C on target cells might directly exert an effect on their infectability by human immunodeficiency virus (HIV) has been suggested previously. This was tested by exploiting the peculiar specificity of monoclonal antibody (mAb) L31 for HLA-C open conformers to show that normal levels of Env-driven fusion were restored in HLA-C transfectants of a major histocompatibility complex-deleted (fusion-incompetent) cell line. The physiological relevance of this finding is now confirmed in this report, where small interfering RNA (siRNA) technology was used to silence HLA-C expression in peripheral blood lymphocytes (PBLs) from 11 healthy donors. Infectability by HIV (strains IIIB and Bal and primary isolates) was significantly reduced (P50.016) in silenced cells compared with cells that maintained HLA-C expression in 10 of the 11 PBL donors. Normal infectability was resumed, together with HLA-C expression, when the effect of siRNA interference waned after several days in culture. Additional confirmation of the HLA-C effect was obtained in several assays employing HLA-C-positive and -negative cell lines, a number of HIV strains and also pseudoviruses. In particular, viruses pseudotyped with env genes from HIV strains AC10 and QH0692.42 were assayed on siRNA-silenced lymphocytes from three healthy donors: the differences in infection with pseudoviruses were even higher than those observed in infections with normal viruses. INTRODUCTIONThree recent whole-genome association studies have demonstrated and confirmed that minor allele variants of singlenucleotide polymorphisms in the major histocompatibility complex (MHC; in particular HLA-C) gene regions are associated with a lower viral load at the set point and additionally with delayed human immunodeficiency virus type 1 (HIV-1) disease progression (Fellay et al., 2007;Limou et al., 2009;van Manen et al., 2009). These findings, which echo a previous report on the association between HLA-C alleles and rapid progression to AIDS (Carrington et al., 1999), have prompted wide speculations on the role of HLA (and HLA-C in particular) in HIV biology and immunology. HLA-C differs from HLA-A and -B because HIV-1 selectively downregulates HLA-A and -B, but does not significantly affect HLA-C (or HLA-E). Therefore, infected cells display reduced detection by both cytotoxic lymphocytes and natural killer (NK) cells (Cohen et al., 1999). The hypothesis that HLA-C might exert an effect directly on HIV infectivity was originally suggested by De Santis et al. (1996), exploiting the peculiar specificity of monoclonal antibody (mAb) L31 to show that normal levels of Env-driven fusion were restored in HLA-C transfectants (Grassi et al., 1991;Setini et al., 1996) of an MHC-deleted (fusion-incompetent) cell line. The physiological relevance of this finding is confirmed in this report, where small interfering RNA (siRNA) technology was used to silence HLA-C expression in peripheral blood lymphocytes (PBLs), the natural target of HIV-1. Two different kinds o...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Hla-c Sirna Silencing In Cell Linesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

Baroni

Matucci

Scarlatti

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

show abstract

MHC‐I recognition by receptors on myelomonocytic cells: New tricks for old dogs?

Raine

Allen

2005

BioEssays

View full text Add to dashboard Cite

Receptors on cytotoxic T lymphocytes and natural killer cells play well-established roles in the immunological response and share a common ligand in the form of MHC-I. We discuss how a variety of MHC-I receptors are also expressed on myelomonocytic cells such as macrophages and dendritic cells. Since myelomonocytic MHC-I receptors recognise a broad range of alleles and MHC-I structures, we propose that their task is to discern expression levels and folding forms of MHC. We describe a model in which these recognition events would regulate bidirectional cross talk between cells of innate and adaptive immune systems to organise an ongoing combined immune response. We discuss how such a model is supported by recent literature and might function in a variety of contexts, including immunoregulation during pregnancy. Our model also offers an alternative explanation of immune dysregulation rather than autoimmunity during HLA-B27-associated spondyloarthropathies and addresses a number of conundrums in this field.

show abstract

Impaired spontaneous endocytosis of HLA‐G

et al. 1997

View full text Add to dashboard Cite

HLA-G is a class Ib (non-classical) major histocompatibility complex (MHC) protein expressed at the maternal-fetal interface that inhibits natural killer (NK) cell-mediated lysis in an allotype-independent manner. Here we report that the spontaneous endocytosis of HLA-G is severely reduced because of its short cytoplasmic tail. Class I (classical) MHC proteins on the surface of B cell transfectants detected by primary and secondary antibodies underwent endocytosis at a moderate rate, whereas HLA-G, chimeric proteins consisting of the extracellular domains of HLA-C with the C-terminal sequence of HLA-G, or glycophosphatidylinositol-tailed HLA-C proteins, were not efficiently internalized. In addition, a mutant of beta 2-microglobulin (Ser88Cys) that could be specifically labeled with Texas red (or other fluorescent probes) and exchanged into class I or class Ib MHC proteins was employed to study spontaneous internalization of MHC proteins by a non-perturbative method independent of an antibody ligand. These data are discussed in terms of both the role of HLA-G expressed on the fetal trophoblast and the function of the cytoplasmic tail in class I MHC proteins.

show abstract

Distinctive Features of the α1-Domain a Helix of HLA-C Heavy Chains Free of β2-Microglobulin

Cited by 61 publications

References 25 publications

HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

MHC‐I recognition by receptors on myelomonocytic cells: New tricks for old dogs?

Impaired spontaneous endocytosis of HLA‐G

Contact Info

Product

Resources

About