Antigen processing for MHC class I restricted presentation of exogenous influenza A virus nucleoprotein by B-lymphoblastoid cells

Voeten, J.T.M.; Rimmelzwaan, Guus F.; Nieuwkoop, Nella J.; Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.

doi:10.1046/j.1365-2249.2001.01613.x

Cited by 17 publications

(15 citation statements)

References 52 publications

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“…Of the 7 directly discovered influenza A virus ligands, only the NP 418-426 peptide contains the I-A b binding motif. However, it is unlikely that the NP 418-426 IFN-␥ response generated by lymphocytes isolated from PR8 infected HLA-B*0702 transgenic mice is largely because of CD4 T cell reactivity given that the NP 418-426 epitope elicits CD8 T cell reactivity during in vitro stimulation of human peripheral blood mononuclear cells (PBMC) isolated from healthy HLA-B*0702 and -B*3501 adults (13,(22)(23)(24).…”

Section: Comparative Mass Spectrometry Reveals 7 Influenza Hla B*0702mentioning

confidence: 99%

HLA class I molecules consistently present internal influenza epitopes

Wahl¹,

Schafer²,

Bardet³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Section: Comparative Mass Spectrometry Reveals 7 Influenza Hla B*0702mentioning

confidence: 99%

HLA class I molecules consistently present internal influenza epitopes

Wahl¹,

Schafer²,

Bardet³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Next, the cells were incubated with a 10-fold serial dilution of the peptides in R10F for 1 h at 37°C, washed once in R10F, and used as target cells in a 51 Cr release assay. The HLA-A2-, -A3-, -B27-, and -B35-restricted influenza A virus-specific CTL clones were previously described (23)(24)(25), while the HLA-A1-and -B8-restricted influenza A virus-specific CTL clones were established, as described previously (25).…”

Section: Preparation Of Target Cells For 51 Cr Release Assaymentioning

confidence: 99%

Preferential HLA Usage in the Influenza Virus-Specific CTL Response

Boon

Mutsert

Fouchier

et al. 2004

The Journal of Immunology

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To study whether individual HLA class I alleles are used preferentially or equally in human virus-specific CTL responses, the contribution of individual HLA-A and -B alleles to the human influenza virus-specific CTL response was investigated. To this end, PBMC were obtained from three groups of HLA-A and -B identical blood donors and stimulated with influenza virus. In the virus-specific CD8+ T cell population, the proportion of IFN-γ- and TNF-α-producing cells, restricted by individual HLA-A and -B alleles, was determined using virus-infected C1R cells expressing a single HLA-A or -B allele for restimulation of these cells. In HLA-B*2705- and HLA-B*3501-positive individuals, these alleles were preferentially used in the influenza A virus-specific CTL response, while the contribution of HLA-B*0801 and HLA-A*0101 was minor in these donors. The magnitude of the HLA-B*0801-restricted response was even lower in the presence of HLA-B*2705. C1R cells expressing HLA-B*2705, HLA-A*0101, or HLA-A*0201 were preferentially lysed by virus-specific CD8+ T cells. In contrast, the CTL response to influenza B virus was mainly directed toward HLA-B*0801-restricted epitopes. Thus, the preferential use of HLA alleles depended on the virus studied.

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“…The EBNA3C epitope becomes readily available for CTL recognition when inserted into the context of the nucleoprotein, thus suggesting the presence in the C terminus of sequences relevant for localization and/or processing by resident proteases. It has been already reported that the epitope 383-391 from the nucleoprotein of influenza A virus can be processed and presented in TAP-deficient cells (38). Moreover, other epitopes carried by this protein appear to follow different routes for processing (13).…”

Section: Discussionmentioning

confidence: 95%

The C Terminus of the Nucleoprotein of Influenza A Virus Delivers Antigens Transduced by Tat to thetrans-Golgi Network and Promotes an Efficient Presentation through HLA Class I

Bettosini

Fiorillo

Magnacca

et al. 2005

J Virol

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Cytotoxic T lymphocytes (CTLs) are the most powerful weapon of the immune system to eliminate cells infected by intracellular parasites or tumors. However, very often, escape mechanisms overcome CTL immune surveillance by impairing the classical HLA class I antigen-processing pathway. Here, we describe a strategy for CTL activation based on the ability of Tat to mediate transcellular delivery of viral proteins encompassing HLA class I-restricted epitopes. In this system, the recombinant protein TAT-NpFlu containing the transduction domain of Tat of human immunodeficiency virus type 1 fused to the amino acid region 301 to 498 of the nucleoprotein of influenza A virus is proven to sensitize different human cells to lysis by HLA-B27-restricted, Flu 383-391-specific CTL lines. The fusion protein is processed very effectively, since a comparable biological effect is obtained with an amount of protein between 1 and 2 orders of magnitude lower than that of the synthetic peptide. Interestingly, while part of TAT-NpFlu undergoes fast and productive cleavage, a large amount of it remains intact for up to 24 h. Confocal microscopy shows that TAT-NpFlu accumulates in the trans-Golgi network (TGN), where it starts to be detectable 1 h after transduction. Using TAT-NpFlu mutants and hybrid constructs, we demonstrate that enrichment in the TGN occurs only when the carboxy-terminal region of NpFlu (amino acids 400 to 498) is present. These data disclose an unconventional route for presentation of epitopes restricted for HLA class I molecules.Cytotoxic T lymphocytes (CTLs) are key cells in immune defense against virus-infected or -transformed cells. However, very often, escape mechanisms overcome CTL immune surveillance by impairing the classical HLA class I antigen-processing pathway (10, 15). There is therefore a great interest in identifying novel routes for presentation on HLA class I molecules to be targeted for immunotherapy.For a long time it was believed that the strict division of HLA class I and class II processing was necessary to identify different physiological responses of the immune system to endogenous (HLA class I) or internalized (HLA class II) proteins. However, although exogenous proteins are normally excluded from presentation by HLA class I molecules, exceptions to this rule have been described in the last 10 years that indicate the possibility, in given circumstances, of engagement and presentation of exogenous antigens on HLA class I molecules either in vivo or in vitro (16,26). In this respect, the immunological meaning of exogenous and endogenous processing should be reevaluated, since several examples of CTLs primed in vivo by proteins present in extracellular fluids have been provided previously (27), and a different pathway for exogenous proteins could be a possible explanation. Moreover, this pathway could be the initiating step for CTL activation in antitumoral immunity and, eventually, parasite infections through cross-priming. Two mechanisms have been suggested to explain exogenous peptide loadin...

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Antigen processing for MHC class I restricted presentation of exogenous influenza A virus nucleoprotein by B-lymphoblastoid cells

Cited by 17 publications

References 52 publications

HLA class I molecules consistently present internal influenza epitopes

HLA class I molecules consistently present internal influenza epitopes

Preferential HLA Usage in the Influenza Virus-Specific CTL Response

The C Terminus of the Nucleoprotein of Influenza A Virus Delivers Antigens Transduced by Tat to thetrans-Golgi Network and Promotes an Efficient Presentation through HLA Class I

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