Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains.

Grassi, Fabio; Meneveri, Raffaella; Gullberg, Martin; Lopalco, Lucia; Rossi, G.; Lanza, Paola; Santis, Claudio De; Brattsand, Göran; Buttò, Stefano; Ginelli, Enrico

doi:10.1084/jem.174.1.53

Cited by 100 publications

(45 citation statements)

References 35 publications

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“…The efficacy of acid-elution was checked by immunofluorescence and flow cytometry using the W6/32 mAb (specific for the trimeric complex of HLA class I) and the HC10 mAb (specific for a common determinant of free HLA heavy chains) [Stam et al, 1990]. The modulation of the expression of HLA-C was then analyzed on cells treated using the citrate buffer and L31 mAb (kindly provided by C. De Santis, HSR, Milan, Italy, specific for the free heavy chain of HLA-C) [Grassi et al, 1991]. The immunofluorescence tests were carried out as follows.…”

Section: Quantitative Expression Of Surface Molecules On Hufmentioning

confidence: 99%

Natural killer cells lyse autologous herpes simplex virus infected targets using cytolytic mechanisms distributed clonotypically

et al. 2000

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Natural killer (NK) cells have the capability of lysing targets that have down-regulated the expression of HLA class I molecules. Herpes simplex virus (HSV) infection results in a profound reduction of HLA class I molecules on the surface of infected cells. For this reason, NK cell populations kill efficiently HSV-infected cells. The recent availability of a panel of monoclonal antibodies directed to NK receptors for HLA class I (CD158a, CD158b, anti-p70, anti-p140, and CD94) allowed an accurate dissection of the NK cell subpopulations. Using this approach, the relationship between the expression of NK cell receptors and the capability of lysing HSV-infected cell targets was analyzed at the clonal level. NK cell clones were derived from healthy donors, and cytolytic properties were assayed against HSV-infected autologous fibroblasts. NK cell clones, classified according to the expression of natural killer-cell receptors on their surface, displayed a great heterogeneity of cytolytic properties against HSV-infected cells. Nevertheless, a more accurate functional analysis demonstrated not only that HSV infection downregulated the expression of HLA-A and HLA-B and did not modify the expression of HLA-C, but also that NK cell clones expressing the "activating" form of the anti HLA-C NK cell receptor were more cytolytic than other clones. This finding suggests that two different and clonally distributed mechanisms of NK cell activation may be employed by NK cells to kill HSV-infected autologous target cells.

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Section: Quantitative Expression Of Surface Molecules On Hufmentioning

confidence: 99%

Natural killer cells lyse autologous herpes simplex virus infected targets using cytolytic mechanisms distributed clonotypically

et al. 2000

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“…HLA-A, B, C, E, and G HC (15,16); the mAb TP25.99 (IgG1) which recognizes distinct determinants expressed on all ␤ 2 m-associated HLA-A, B, C, and E HC and on all ␤ 2 m-free HLA-A, B, C HC except A2, A10, A29, A31, 32, 33, A68.1, A69, and B73 (4,17); and the mAb L31 (9,12) which recognizes a determinant preferentially expressed on ␤ 2 m-free HLA-B HC were produced and characterized as previously described. The BALB/c mouse mAb 655 (IgG1) and its corresponding Ag, the human V␤-17 TCR-derived peptide GYSVSREKKES (p-V␤17), were used as controls.…”

Section: Cellsmentioning

confidence: 99%

“…Whether this lack of reactivity reflects changes in the antigenic profile caused by the structural changes induced by association with ␤ 2 m and/or steric hindrance because of close proximity of the antigenic determinant with the areas of the HC occupied by the peptide located in the HLA-I groove is not known. Like the mAb LA45 (8), L31 (9), and HCA2 (10), which also react with ␤ 2 m-free HLA-I HC only, mAb HC-10 reacts with many, but not with all HLA-I HC (7,11,12). In addition, the epitope it recognizes appears to be involved in the pathogenesis of human-like spondyloarthropathies, because administration of mAb HC-10 reduces the incidence of the disease in B27 ϩ ␤ 2 m°/MHC class II knockout (A␤°) mice (13).…”

mentioning

confidence: 99%

β2-Microglobulin-Free HLA Class I Heavy Chain Epitope Mimicry by Monoclonal Antibody HC-10-Specific Peptide

Perosa

Luccarelli

Prete

et al. 2003

The Journal of Immunology

150

163

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mAb HC-10 loses its reactivity with HLA class I (HLA-I) H chain (HC) following its association with β2-microglobulin (β2m). Furthermore, the HC-10 defined epitope appears to be involved in the pathogenesis of spondyloarthropathies, because HC-10 reduced their incidence in HLA-B27+β2m°/MHC class II knockout mice. This study has characterized the determinant recognized by HC-10. Panning of a phage display peptide library with HC-10 resulted in isolation of the motif PxxWDR, which could be aligned with P57, W60, D61, and R62 of the first domain of the HLA-I HC allospecificities reactive with HC-10. The 55EGPEYWDR(N/E)T64 (p-1) is the shortest motif-bearing peptide that reacts with HC-10 and inhibits its binding to soluble HLA-B7 HC, irrespective of whether N (p-1a) or E (p-1b) is present at position 63. By contrast, HC-10 did not react with six additional peptides, each bearing motif amino acid substitutions present in HC-10-not-reactive HLA-I allospecificities. The p-1-derived Qp-1, synthesized with the additional conserved Q54, which displays the highest in vitro reactivity with HC-10, was the only one to induce in mice IgG resembling HC-10 in their fine specificity. Mapping of the HC-10-defined determinant suggests that the lack of mAb reactivity with β2m-associated HLA-I HC is caused by blocking by the peptide in the groove of β2m-associated HLA-I HC, though a role of HC conformational changes following its association with β2m cannot be excluded. This information contributes to our understanding of the molecular basis of the antigenic profiles of β2m-free and β2m-associated HLA-I HC and may serve to develop active specific immunotherapy of spondyloarthropathies.

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“…After 45 minutes of incubation 125 I-MIP1␤ (Dupont-NEN, Mechelem, Belgium) or 125 I-MCP1 (Amersham) was added [final concentration 0.1 nM, 0.2 Ci (0.0074 MBq)], and incubation at 4°C was continued for an additional 2 hours. Unbound radioactivity was separated from cell-bound radioactivity by centrifugation in an Eppendorf centrifuge on a 2-step gradient 28 in 0.3-mL tubes (Nunc, Roskilde, Denmark) where the lower layer consisted of fetal calf serum (FCS) containing 10% sucrose and the upper layer consisted of 80% silicone (Sigma-Aldrich) and 20% mineral oil (Sigma-Aldrich). The bound radioactivity in the cell pellets was measured in a gamma scintillator counter (Perkin Elmer, Turku, Finland).…”

Section: Study Populationmentioning

confidence: 99%

Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression

Pastori¹,

Weiser

Barassi

et al. 2006

Blood

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Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whether anti-CCR5 antibodies may also contribute to slow HIV disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 longterm nonprogressors (LTNPs), 70 progressors, 135 HIV ؉ patients treated with highly active antiretroviral therapy (HAART), and 207 seronegative donors. We found anti-CCR5 antibodies in a fraction of the LTNPs (23.5%) but not in the other populations studied (P < .001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5, and they induced a stable and long-lasting downregulation of CCR5 on the surface of T lymphocytes, which inhibited HIV entry. In addition, CD4 ؉ lymphocytes from LTNPs having anti-CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects, and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti-CCR5 Abs maintained their LTNP status. Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics.

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Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains.

Cited by 100 publications

References 35 publications

Natural killer cells lyse autologous herpes simplex virus infected targets using cytolytic mechanisms distributed clonotypically

Natural killer cells lyse autologous herpes simplex virus infected targets using cytolytic mechanisms distributed clonotypically

β2-Microglobulin-Free HLA Class I Heavy Chain Epitope Mimicry by Monoclonal Antibody HC-10-Specific Peptide

Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression

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