Viral immunology

Research summary:

Our field of interest is aimed at improving the control of chronic and opportunistic infections by the immune system, for which the cellular immune response, as opposed to antibodies alone, plays a leading role, with the long-term goal of contributing to an improved design of new vaccines. Although much is known, vaccines inducing a potent and long-lasting T-cell immunity are still not available. Beyond childhood-oriented vaccines, and due to recent demographic changes and medical advances, the focus of vaccine development is shifting to the new needs of protecting a growing number of adult patients with diverse congenital (primary immunodeficiencies) or iatrogenic levels of immunosuppression (cancer, organ transplantation, autoimmunity) or in specific stages of life (pregnancy, elderly). In order to adapt basic research to these changing needs, we are analyzing basic issues of antiviral cellular immune responses and vaccination in two models of partially immunocompromised mice.

Our first model are mice deficient in the transporter associated with antigen processing (TAP), a crucial player in the MHC class I antigen presentation pathway for recognition by CD8+ T lymphocytes, which are the effector cells responsible for the elimination of infected cells in vivo. These mice are a model for TAP-deficient patients, who suffer from severe recurrent bacterial infections, and have a strong quantitative defect in CD8 cellular immunity, although the remaining CD8+ T lymphocytes are functional. We are currently identifying MHC-I presented viral peptide epitopes, the proteases and the antigen processing pathways generating them in infected cells and trying to elucidate their contribution to the CD8 immune response in these animals.

The second model is represented by mice deficient for the Nras signaling protein, which we have shown to have a qualitative Eomes defect that precludes development of anti-viral memory CD8+ T lymphocytes, and thus prevents vaccination. We are currently evaluating vaccination procedures that could overcome this defect and that might be applied to vaccine design.

The viral infection models we are using are vaccinia virus and mouse cytomegalovirus. Vaccinia virus, a poxvirus, is the vaccine vector behind the first and major success of vaccinology in public health: the eradication of smallpox, officially declared in 1980. Cytomegalovirus is relevant for vaccine design, as it remains latent and continuously presents antigen without pathology, which leads for life to a massive number of functional virus-specific T lymphocytes in the infected organisms, called inflationary memory.

Image

Figure 1. MHC class I viral antigen processing and presentation pathway. The left panel shows the central role played by TAP transporter in this pathway, translocating peptides as well as serving as the hub for the assembly of the peptide loading complex (PLC). The right panel shows the impact of TAP inactivation on MHC class I antigen presentation. The panel also points to potential routes that may mediate the processing of MHC class I antigenic peptides that, although at low levels, are presented by MHC class I in these cells.

Image

Figure 2. Generation of memory CD8+ cytotoxic T lymphocytes. The left panel shows the T cell receptor (TCR) signaling pathway mediated by Nras that results in the induction of the transcription factor Eomes, which promotes differentiation to memory T lymphocytes. The right panel shows the effect of inactivating Nras in T lymphocytes, which results in a compromised function of Eomes and, consequently a defective memory CD8+ T lymphocyte immune response.

Image


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Antón CantoLuis Carlos2044553lanton(at)cbm.csic.esE.Científicos Titulares de Organismos Públicos de Investigación
Campos SánchezElena2044461ecampos(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1 Indef.
Canto MéndezAndrea2044461acanto(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1 Indef.
Mena RomeroBeatriz2044461bmena(at)cbm.csic.esGJ-AI y TL_Técnico Sup. Actividades Técn. y Prof.GP3
Muñoz AbadVíctor2044461victor.munoz(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Ramos Alvarez-BuyllaManuel2044461mbuylla(at)cbm.csic.esE.Científicos Titulares de Organismos Públicos de Investigación
Rodríguez RojasCristina2044461cristina.rrojas(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Soto ZaragozaAndrés2044461Becario JAE Intro
Tejedor Sáez-BravoBeatriz2044461btejedor(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Val LatorreMargarita del2044460mdval(at)cbm.csic.esE. Investigadores Científicos de Organismos Públicos

Relevant publications:

  • M. Del Val, L.C. Antón, M. Ramos, V. Muñoz-Abad, E. Campos-Sánchez, Endogenous TAP-independent MHC-I antigen presentation: not just the ER lumen, Curr. Op. Immunol. 64 (2020) 9-14.
  • J. Navarro, B. Gozalbo-López, A.C. Méndez, F. Dantzer, V. Schreiber, C. Martínez, D.M. Arana, J. Farrés, B. Revilla-Nuin, M.F. Bueno, C. Ampurdanés, M.A. Galindo-Campos, P.A. Knobel, S. Segura-Bayona, J. Martin-Caballero, T.H. Stracker, P. Aparicio, M. Del Val, J. Yélamos, PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas, Sci. Rep. 7(1) (2017) 41962.
  • M. Ramos, Y. Lao, C. Eguiluz, M. Del Val, I. Martínez, Urokinase receptor-deficient mice mount an innate immune response to and clarify respiratory viruses as efficiently as wild-type mice, Virulence 6(7) (2015) 710-715.
  • L.C. Antón, J.W. Yewdell, Translating DRiPs: MHC class I immunosurveillance of pathogens and tumors, J. Leuk. Biol. 95(4) (2014) 551-562.
  • S. Iborra, M. Ramos, D.M. Arana, S. Lázaro, F. Aguilar, E. Santos, D. López, E. Fernández-Malavé, M. Del Val, N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T cell memory but not to effector differentiation, J. Exp. Med.210(7) (2013) 1463-1479.
  • M. Buxadé, G. Lunazzi, J. Minguillón, S. Iborra, R. Berga-Bolaños, M. del Val, J. Aramburu, C. López-Rodríguez, Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5, J. Exp. Med.  209(2) (2012) 379-393.
  • P.S. Satheshkumar, L.C. Anton, P. Sanz, B. Moss, Inhibition of the Ubiquitin-Proteasome System Prevents Vaccinia Virus DNA Replication and Expression of Intermediate and Late Genes, J. Virol. 83(6) (2009) 2469-2479.
  • F. Medina, M. Ramos, S. Iborra, P. de León, M. Rodríguez-Castro, M. Del Val, Furin-Processed Antigens Targeted to the Secretory Route Elicit Functional TAP1−/−CD8+ T Lymphocytes In Vivo, J. Immunol. 183(7) (2009) 4639-4647.
  • L. Saveanu, O. Carroll, V. Lindo, M. Del Val, D. Lopez, Y. Lepelletier, F. Greer, L. Schomburg, D. Fruci, G. Niedermann, P.M. van Endert, Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum, Nature Immunol. 6(7) (2005) 689-697.
  • B.C. Gil-Torregrosa, A.R. Castano, M. Del Val, Major histocompatibility complex class I viral antigen processing in the secretory pathway defined by the trans-Golgi network protease furin, J. Exp. Med. 188(6) (1998) 1105-1116.

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand

COOKIES POLICY

What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: