Celular Immunology

IBB > Research > Response Mechanisms to Stress and Disease > Celular Immunology

Jaraquemada Perez de Guzman, Dolores
935812409 Dolores.jaraquemada@uab.es ibb.uab.cat/wp-content/themes/viral/modules/ibb_membres/view_grup.php?CodiGrup=31

Research lines

Dr. Dolores Jaraquemada

Protein autoantigens in Type 1 Diabetes

Respect to the recognition of proteins by T cells, our approach, following our previous experience with T1D and other autoinmune diseases, is to find T cell ligands that are present in the periphery but are not found in the thymus. Thus, we seek to identify CD4+ and CD8+ T cell epitopes for which there is a deficient central tolerance. Our approach includes two steps:

Peptidome of pancreatic b cells. Comparison with thymic natural peptide repertoires. We are aiming at the ex vivo identification of peptides presented by MHC class I and class II molecules from pancreatic b cells and thymus from donors matching relevant MHC class I and II alleles. We will also analyze the peptides presented by dendritic cells from healthy donors expressing T1D-associated HLA alleles pulsed with b-cells protein extracts and/or soluble autoantigens. T cell reactivity to the identified natural ligands will be screened.

Is there a differential peptide repertoire presented by MHC-II molecules in the cortex and the medulla of the thymus? Immunoproteomic analysis of the peptide repertoire participating in positive and negative selection in the thymus upon tissue microdissection. Searching for the b cell-specific peptides identified in the thymic medulla.

Research lines of Dr. Carme Roura-Mir

Dr. Carme Roura-Mir

Lipid autoantigens in human type I Diabetes

Insulin-specific autoreactive CD8+ and CD4+ T cells are key at driving the autoimmune response in Type 1 Diabetes. Other antigenic specificities can be equally important along disease development or maintenance. Most of these proteins reside in the insulin secretory granules or the crinophagic bodies of β cells. There are a few reports on MHC class I presented peptides in human T1D. Much less is known on CD4+ effector or regulatory T cell recognized peptides in human T1D.

Apart from proteins, lipid-based antigens can load on MHC-I non-classical CD1 molecules and be recognized by NKT cells. Both exogenous and endogenous lipids have been shown to gain access to intracellular compartments and intersect CD1 molecules. However, the target ligands recognized by these cells in the autoimmune context are barely known. Further, little is known about local lipid ligands for NKT cells that may be influencing the disease outcome. The group is working on two different aspects:

The regulatory role of iNKT cells in Type 1 Diabetes

NKT cells regulate effector T cells in an IL13 dependent manner. In T1D patients NKT cells seem to lose their regulatory capacity which can be associated to a poor IL13 production at disease onset. Usero et al. Diabetes 2016;65:2356–66.

The regulatory deficiency of NKT cells in T1D patients can be related to a differentiated gene expression pattern compared to NKT cells from healthy controls (ongoing research).

Lipid-based autoantigens recognized by iNKT cells in T1D

Because of their secretory function, b cells have a highly developed ER and are highly susceptible to ER stress. The group studies if cellular stress alters b cells lipid content generating lipid antigens that activate iNKT cells.

Response to b cell lipid extracts

Research lines of Dr. Mercè Martí

Dr. Mercè Martí is running two parallel lines of research.

Characterization of infiltrating T lymphocytes in samples of breast cancer (BREASTILs). T-cells are studied by i) molecular and functional level, ii) TCR diversity and clonality and iii) peptide repertoire presented by dendritic cells pulsed with tumor tissue. This project is in collaboration with Dr. Javier Cortés VHIO researcher.

Design of biosensors in the field of biomedicine (EXOSENS). This project is in collaboration with Dra. Maria Isabel Pividori of the Dp. of Chemistry at the UAB. We have designed a magnetoELISA and an electrochemical ELISA for the detection of exosomes from serum or plasma samples from breast cancer patients (doi: 10.1016/j.talanta.2019.120657; doi: 10.1016/j.bios.2019.111882) and from Alzheimer patients (in collaboration with ACE Foundation). We are also interested in biosensors for immunological biomarkers as cytokines. We have developed a genosensor (doi: 10.1016/j.bios.2018.05.030) and a rapid flow test (lateral flow) for the detection of proinflammatory cytokines in the context of infectious diseases as tuberculosis or COVID 19.

Research lines of Iñaki Alvarez

The current lines of Iñaki Alvarez are:

Study of the specificity and contribution on the HLA peptide repertoires of different proteasomes and its role in tolerance and disease.
Analysis of the role of the autoimmune regulator (AIRE) in antigen expression, processing and presentation.
Study of standard and post-translational modificated HLA ligands in tolerance and disease.

Group members

Head of the Group:

Jaraquemada Perez de Guzman, Dolores

Members:

Muntasell Castellví, Aura

Area Navarro, María

García AYALA, Manel

Lázaro Bermejo, Gonzalo

Pastor Moreno, Alba

Tirado Herranz, Adrián

Pacios Pujado, Carme

Alvarez Perez, Iñaki

Roura , Carme

Publications

Roura-Mir, C., Catalfamo, M., Cheng, T. Y., Marqusee, E., Besra, G. S., Jaraquemada, D., and Moody, D. B. (2005) Journal of Immunology 174, 3773-3780.

Blanco, Y., Saiz, A., Costa, M., Torres-Peraza, J. F., Carreras, E., Albrech, J., Jaraquemada, D., and Graus, F. (2005) Neuroscience Letters 380, 122-126.

Saiz, A., Carreras, E., Torres-Pefaza, J., Costa, M., Alberch, J., Jaraquemada, D., and Graus, E. (2004) Multiple Sclerosis 10, S168-S168.

Muntasell, A., Carrascal, M., Alvarez, I., Serradell, L., van Veelen, P., Verreck, F. A. W., Koning, F., Abian, J., and Jaraquemada, D. (2004) Journal of Immunology 173, 1085-1093.

Garavito, G., Yunis, E. J., Egea, E., Ramirez, L. A., Malagon, C., Iglesias, A., De La Cruz, O. F., Uribe, O., Navarro, E., Martinez, P., and Jaraquemada, D. (2004) Human Immunology 65, 359-365.

Diaz, G., Amicosante, M., Jaraquemada, D., Butler, R. H., Guillen, M. V., Sanchez, M., Nombela, C., and Arroyo, J. (2003) International Immunology 15, 565-576.

Muntasesll, A., Carrascal, M., Serradell, L., van Veelen, P., Verreck, F., Koning, F., Raposo, G., Abian, J., and Jaraquemada, D. (2002) Journal of Immunology 169, 5052-5060.

Fernandez-Mestre, M. T., Jaraquemada, D., Bruno, R. E., Caro, J., and Layrisse, Z. (2002) Tissue Antigens 60, 10-15.

Dodi, I. A., Van Rhee, F., Forde, H. C., Roura-Mir, C., Jaraquemada, D., Goldman, J. M., and Madrigal, J. A. (2002) Cytotherapy 4, 353-363.

Costa, M., Saiz, A., Casamitjana, R., Castaner, M. F., Sanmarti, A., Graus, F., and Jaraquemada, D. (2002) Clinical and Experimental Immunology 129, 471-478.

Serradell, L., Muntasell, A., Catalfamo, M., Marti, M., Costa, M., de Preval, C., and Jaraquemada, D. (1999) Tissue Antigens 53, 447-458.

Kolkowski, E. C., Reth, P., Pelusa, F., Bosch, J., Pujol-Borrell, R., Coll, J., and Jaraquemada, D. (1999) Journal of Autoimmunity 13, 155-162.

Catalfamo, M., Serradell, L., Roura-Mir, C., Kolkowski, E., Sospedra, M., Vives-Pi, M., Vargas-Nieto, F., Pujol-Borrell, R., and Jaraquemada, D. (1999) International Immunology 11, 269-277.

Muntaseil, A., Serradell, L., Catalfamo, M., and Jaraquemada, D. (1998) Diabetologia 41, A100-A100.

Marti, M., Costa, M., Roura-Mir, C., Botello, D., Pujol-Borrell, R., and Jaraquemada, D. (1998) Diabetologia 41, A9-A9.

Dodi, I. A., Van Rhee, F., Roura-Mir, C., Forde, H., Fischer, G., Jaraquemada, D., Goldman, J. M., and Madrigal, J. A. (1998) Bone Marrow Transplantation 21, S66-S66.

Castro, M. J., Morales, P., Catalfamo, M., Fernandez-Soria, V., Suarez, B., Varela, P., Perez-Blas, M., Alvarez, M., Jaraquemada, D., and Arnaiz-Villena, A. (1998) European Journal of Immunogenetics 25, 311-315.

Papadopoulos, K. P., Colovai, A. I., Maffei, A., Jaraquemada, D., SuciuFoca, N., and Harris, P. E. (1996) Diabetes 45, 1761-1765

Funding