Binding of labelled influenza matrix peptide to HLA DR in living B lymphoid cells

Ceppellini, R; Frumento, Guido; Ferrara, Giovanni Battista; Tosi, Roberto; Chersi, Alberto; Pernis, Benvenuto

doi:10.1038/339392a0

Cited by 84 publications

(51 citation statements)

References 21 publications

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“…The association curve of HA 128-145/DRw11 complexes (Fig. 7) shows an appearance of the complex by 30 min that is consistent with previous reports (34,35). The continued complex accumulation to 24 h is longer than that previously reported by Ceppellini et al (34) for living APC's and is consistent with the report of Busch et al .…”

Section: Discussionsupporting

confidence: 80%

“…(12,22), who showed a lack of surface peptide,-class II saturation after 16 h of APC antigen incubation using a biotinylated HA 307-319 peptide on DR1-expressing cells. Studies of peptide saturation using solubilized, purified class II protein have also demonstrated a slow accumulation of the complex peaking at extended intervals of from 6 to 50 h (7,8,34) . The very rapid plateau in binding of radiolabeled peptide on whole B-LCL's reported by Ceppellini et al (34) may be a reflection of cell peptide internalization with the inability of the radiolabel assay to separate surface from internal peptide uptake .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antibody recognition of an immunogenic influenza hemagglutinin-human leukocyte antigen class II complex.

Nygard

Bono

Brown

et al. 1991

The Journal of Experimental Medicine

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SummaryThe A/Japan/57 influenza hemagglutinin (HA) peptide HA 128-145, when bound by human histocompatibility leukocyte antigen-DRw11 cells, is recognized by the human CD4+ T cell clone V1. A rabbit antiserum has been raised against HA 128-145 which recognizes not only the free peptide, but also the HA 128-145/DRw11 complex on a solid matrix, in solution, or on the surface of viable cells. The detection of these complexes on viable cells was shown to be class II specific, DRw11 restricted, and commensurate with the level of DRw11 expression. The identity of DRw11 as the cell surface molecule binding HA 128-145 was confirmed by immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and tryptic peptide mapping. Using this antiserum, HA 128-145/DRw11 complexes could be detected on the cell surface as soon as 30 min after the peptide was added, and increased up to 24 h. Dissociation kinetics showed these complexes were long-lived, with a half-life of approximately 14 h. This anti-HA peptide antiserum represents the first direct means of studying antigenic peptide-human leukocyte antigen class II complexes on the surface ofliving cells without the addition of a nonamino acid moiety to the peptide. The properties of this antiserum thus provide the potential to study naturally processed antigenic peptides as well as the mechanism of processing itself in a physiologically relevant system . T he immune response of CD4+ T cells is thought to be triggered by immunogenic MHC class II moleculepeptide complexes present on the surface of APC's (1-5). Previous reports have demonstrated in vitro association of peptide antigen with purified class II molecules (5-10), and proliferation of cloned T cells exposed to these complexes (6, 11) .While antigen-specific T cells have been useful for qualitatively demonstrating the presence of such complexes, the low number of surface peptide-class II complexes needed to activate a T cell, and the all-or-none nature of the recognition event have made such assays less useful for studying the kinetics and nature ofpeptide-class II binding (12)(13)(14). Studies of APC antigen processing and class II loading have been hampered by the inability to directly detect peptide bound in the antigen-binding groove ofthese molecules on the surface ofintact cells. Whole cell binding assays using radiolabelled peptide antigen have been plagued by nonspecific uptake of radiolabel into the cells . Those studies which promote metabolic antigen-processing have suffered from unacceptably high levels of nonspecific binding which have made it difficult to separately study the complexes of peptide antigen bound to surface class II molecules . Similar studies done under conditions which block APC intracellular antigen uptake and processing have demonstrated a high level of nonspecific cell surface binding and only a low level of binding to class II molecules (7,(15)(16)(17)(18)(19)(20) .A series of rather elegant studies using biotinylated peptides and a fluorescent-avidin detection system h...

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Antibody recognition of an immunogenic influenza hemagglutinin-human leukocyte antigen class II complex.

Nygard

Bono

Brown

et al. 1991

The Journal of Experimental Medicine

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“…First, the antigen-presenting capacity of HLA may differ in relationship to the difference in the binding affinities to HCV antigens. 6,7 In chronic HCV infection, HCV-specific CD4 ؉ or CD8 ؉ T-cell responses play essential roles in the pathogenesis of liver disease. [31][32][33] At the induction phase of these responses, activation signals are transduced to T cells in the context of the HLA-peptide-T-cell receptor complex.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 The associations between HLA polymorphism and disease susceptibility or resistance have been well investigated, especially in autoimmune or metabolic diseases. [8][9][10] Recently, for some viral infections, associations have been reported between HLA polymorphism and the clinical outcome of infected patients.…”

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confidence: 99%

Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus

et al. 1998

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“…(1) Lack of Ir-genes: HLA-class II molecules of nonresponders can not bind processed antigen (Buus et at., 1986;Ceppellini et al, 1989). (2) Cross tolerance: HLA class II molecules of nonresponders share epitopes with antigen in question.…”

Section: Possible Mechanisms Of Nonresponsiveness Controlled By Hla-cmentioning

confidence: 99%

HLA-linkedImmune suppression genes

Sasazuki

1990

Jap J Human Genet

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SummaryGenetic control of immune response was investigated by family and population analyses in humans. It was first recognized that there are high responders and low or non responders to natural antigens in human population. Family analysis revealed that low responsiveness to streptococcal cell wall antigen (SCW) was inherited as an HLA-linked dominant trait. CD8 + suppressor T ceils existed in low responders and depletion of the CD8 + T ceils from low responders could restore the strong immune response to SCW. Therefore the gene controlling the low response to SCW was designated as an immune suppression gene for SCW.Immune suppression gene for SCW was in strong linkage disequilibrium with particular alleles of HLA-DQ locus. The association between HLA-DQ alleles and low responsiveness mediated by CD8 + suppressor T cell was also observed for schistosomal antigen, Myeobacterium leprae antigen, tetanus toxoid, cryptomeria pollen antigen and hepatitis B virus surface antigen suggesting that low responsiveness to those antigens was also controlled by immune suppression genes. Anti-HLA-DR monoclonal antibodies inhibited the immune response to those antigens of high responders in vitro, but anti-HLA-DQ monoclonal antibodies did not. On the other hand, anti-HLA-DQ monoclonal antibodies restored the immune response in low responders. Therefore, it is suggested that HLA-DR upregulates immune response and that HLA-DQ downregulates it and that HLA-DQ is epistatic to HLA-DR in the regulation of immune response in humans. Furthermore, direct evidence for the differential in immune regulation between HLA-DR and DQ was obtained by analyzing the SCW specific T cell lines from low responders. SCW specific and HLA-DQ restricted CD4+ T cell lines could activate CD8 + suppressor T cells which in turn downregulate SCW specific CD4+ T cells whereas SCW specific and HLA-DR restricted CD4 + T cell lines could not activate CD8 + suppressor T cells. All these observation clearly demonstrated that the HLA-linked

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Binding of labelled influenza matrix peptide to HLA DR in living B lymphoid cells

Cited by 84 publications

References 21 publications

Antibody recognition of an immunogenic influenza hemagglutinin-human leukocyte antigen class II complex.

Antibody recognition of an immunogenic influenza hemagglutinin-human leukocyte antigen class II complex.

Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus

HLA-linkedImmune suppression genes

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