Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition.

Binnendijk, Robert S. van; Baalen, Carel A. van; Poelen, Martien C. M.; Vries, Petra de; Boes, Jolande; Cerundolo, Vincenzo; Osterhaus, A. D. M. E.; Uytdehaag, Fons G. C. M.

doi:10.1084/jem.176.1.119

Cited by 121 publications

(59 citation statements)

References 75 publications

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“…We investigated whether binding of MV by LCs results in antigen presentation to MV-specific CD4 1 T cells using the CD4 1 T-cell clone GRIM-F99 that recognizes a peptide derived from the MV envelope glycoprotein F in the context of HLA-DQw1 [30,31]. Activation of the T-cell clone GRIM-F99 does not require full co-stimulation.…”

Section: Captured By Lcs Results In Hla-ii-restricted Antigen Presmentioning

confidence: 99%

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Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation

et al. 2011

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Langerhans cells (LCs) are a subset of DCs that reside in the upper respiratory tract and are ideally suited to sense respiratory virus infections. Measles virus (MV) is a highly infectious lymphotropic and myelotropic virus that enters the host via the respiratory tract. Here, we show that human primary LCs are capable of capturing MV through the C-type lectin Langerin. Both immature and mature LCs presented MV-derived antigens in the context of HLA class II to MV-specific CD4 1 T cells. Immature LCs were not susceptible to productive infection by MV and did not present endogenous viral antigens in the context of HLA class I. In contrast, mature LCs could be infected by MV and presented de novo synthesized viral antigens to MV-specific CD8 1 T cells. Notably, neither immature nor mature LCs were able to cross-present exogenous UV-inactivated MV or MV-infected apoptotic cells. The lack of direct infection of immature LCs, and the inability of both immature and mature LCs to crosspresent MV antigens, suggest that human LCs may not be directly involved in priming MV-specific CD8 1 T cells. Immune activation of LCs seems a prerequisite for MV infection of LCs and subsequent CD8 1 T-cell priming via the endogenous antigen presentation pathway. Eur. J. Immunol. 2011. 41: 2619-2631 DOI 10.1002 Immunity to infection 2619 molecules, a process referred to as cross-presentation which is thought to be important in both viral and tumor immunity [2,3]. It is becoming evident that different DC subsets have specialized functions in anti-viral immunity, e.g. by inducing preferentially CD4 1 or CD8 1 T-cell responses or by inducing innate immunity against pathogens [4,5]. Langerhans cells (LCs) are a subset of DCs that are, in humans, characterized by expression of CD1a, the C-type lectin Langerin and the presence of Birbeck granules [6]. LCs reside in the epidermis and stratified epithelial tissues [7][8][9]. Recently, we have shown that LCs form a barrier against HIV-1; LCs capture HIV-1 through Langerin, resulting in internalization of HIV-1 into Birbeck granules and preventing subsequent HIV-1 transmission [10]. However, little is known about the role of human LCs and Langerin in antigen presentation.Capture of exogenous antigens by LCs leads to induction of CD4 1 T-cell responses [11][12][13]. However, the ability of LCs to cross-present exogenous antigens to CD8 1 T cells has been debated [14][15][16][17]. Klechevsky et al. [13] have shown that in vitrogenerated human LCs from either CD34 1 cells or monocytes are capable of cross-presenting influenza-virus proteins to CD8 1 T cells. However, these in vitro-generated LCs might be different from primary immature LCs.Here, we have investigated the antigen capture and presentation capacity of human primary LCs during measles virus (MV) infection. MV is the causative agent of measles, which remains an important cause of morbidity and mortality in developing countries. MV is a lymphotropic and myelotropic virus and DCs have been implicated in its transmission [18,19]. MV is on...

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Section: Captured By Lcs Results In Hla-ii-restricted Antigen Presmentioning

confidence: 99%

“…The CD4 1 T-cell clone Hd7 [29], CD4 1 T-cell clone GRIM-F99 [30] and the CD8 1 T-cell clone WH-F40 [31] were cultured as described before.…”

Section: Cellsmentioning

confidence: 99%

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation

et al. 2011

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“…Activation of CTL responses by ISCOMs was first reported with HIV gp160-ISCOMs and influenza-ISCOMs [102]. Other antigens that have been shown to induce CTL responses in mice after parenteral administration in ISCOMs include OVA [37,96,103], measles virus F-protein [104], RSV [105], mycobacteria hsp60 [106], SIV proteins [107], and HPV E6 and E7 proteins [108]. Intranasal administration of influenza-ISCOMs or ISCOMs containing a CTL epitope of measles virus nucleoprotein linked to a fusion peptide-induced CTL responses [109,110] as did oral immunization with OVA [96,103,111].…”

Section: Activation Of Ctl Responsesmentioning

confidence: 99%

“…Binnendijk et al [104] showed that ISCOMs containing the measles virus F protein sensitized target cells for lysis by CD8 ϩ MHC class I-restricted CTL clones. Sensitization was dependent on cytosolic processing of the F protein to generate peptides presented by MHC class I molecules.…”

Section: Activation Of Ctl Responsesmentioning

confidence: 99%

ISCOMs: an adjuvant with multiple functions

Sjölander

Cox

Barr

1998

Journal of Leukocyte Biology

158

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“…1 TCC recognize MV-infected B-LCL whereas CD4 1 TCC can recognize either MV-infected or antigenpulsed B-LCL [24]. The virus suppression assay as described here has several advantages over the more traditional methods to study cellular immunity: it directly assesses antiviral activity rather than parameters that are associated with the antiviral capacity, like IFN-g production or cytolytic activity.…”

Section: Infectionmentioning

confidence: 99%

Specific CD8⁺ T‐lymphocytes control dissemination of measles virus

et al. 2010

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Measles continues to be an important cause of childhood mortality in developing countries. Measles virus (MV) is lymphotropic and infects high percentages of B-and T-lymphocytes in lymphoid tissues. Cellular immunity is considered crucial for viral clearance; however, MV-specific T-lymphocytes generated during primary infection also constitute a potential target for MV infection. We therefore aimed to identify T-lymphocyte subsets that can clear MV infection without becoming infected. To this end, we infected human EBV transformed B-lymphoblastic cell lines (B-LCL) with a recombinant MV strain expressing enhanced GFP, and co-cultured these with non-infected B-LCL resulting in rapid viral spread. MV-specific CD8 1 T-cell clones efficiently suppressed MV dissemination in autologous and HLA-matched, but not in HLA-mismatched B-LCL. In contrast, CD41 T-cell clones could not control MV dissemination but became a target for MV infection themselves. Furthermore, PBMC collected 6-9 months after acute measles and stimulated with autologous MV-infected B-LCL also efficiently suppressed MV dissemination; this was mediated by the fraction containing CD8 1 T-lymphocytes. In conclusion, we have developed a powerful tool to study cellular immunity against measles, and demonstrate that control of MV dissemination is mediated by virus-specific CD8 1 rather than by CD4 1 T-lymphocytes.Key words: Clearance . Measles virus . Suppression . T-lymphocytes IntroductionDespite significant progress of global control programs, measles continues to be an important cause of morbidity and mortality in developing countries. Measles virus (MV) is a highly contagious agent that is transmitted by aerosols or direct contact with contaminated respiratory secretions. Measles starts with a prodromal phase of fever, cough and coryza, followed by a generalized maculopapular skin rash and conjunctivitis [1]. This phase is associated with a transient but profound immune suppression that can persist for months after convalescence, resulting in an increased susceptibility to opportunistic infections.Paradoxically, measles also induces strong MV-specific humoral and cellular immune responses, resulting in lifelong immunity [2]. Virus neutralizing serum antibodies are considered the main correlate of protection against MV infection [3]. However, viral clearance is predominantly mediated by cellular immune responses. This is illustrated by the fact that hypogammaglobulinemic children recover normally from MV infection [4,5], whereas children with deficits in cellular immunity develop severe disease and display prolonged viral shedding [4,6,7]. This could be partly due to the spread of MV via cell-cell fusion, thus potentially avoiding neutralizing antibodies in the bloodstream. Ex vivo experiments have shown that CD81 MV-specific Currently, most studies on antiviral cellular immunity focus on quantification of virus-specific T cells rather than on the functional capacity of these cells. These assays either assess lymphoproliferation (e.g. CFSE dilution assay...

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Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition.

Abstract: SummaryThe routes used by antigen-presenting cells (APC) to convert the transmembrane fusion glycoprotein

Cited by 121 publications

References 75 publications

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation

ISCOMs: an adjuvant with multiple functions

Specific CD8⁺ T‐lymphocytes control dissemination of measles virus

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Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition.

Abstract: SummaryThe routes used by antigen-presenting cells (APC) to convert the transmembrane fusion glycoprotein

Cited by 121 publications

References 75 publications

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4+ T cells but are incapable of cross‐presentation

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4+ T cells but are incapable of cross‐presentation

ISCOMs: an adjuvant with multiple functions

Specific CD8+ T‐lymphocytes control dissemination of measles virus

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Product

Resources

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Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation

Specific CD8⁺ T‐lymphocytes control dissemination of measles virus