22 sept. 2013

FINAL CliNK MEETING, JUNE 17-18, 2013

The last CliNK meeting took place in Madrid on 17-18 June.
Organized by Carlos Vilches, from Hospital Puerta de Hierro.
The last CliNK meeting took place in Madrid on 17-18 June, organized by Carlos Vilches, from Hospital Puerta de Hierro. 

Monday

1. After opening of the meeting and welcome by the organizer, the coordinator, Alberto Anel, on behalf of Oswaldo Somolinos, informed the group of the next administrative steps and actions to be taken, and of the end of the project by June 30th. A general perspective of the goals achieved was also provided. This led to a series of talks by each group, on different topics related to the project objectives:

2. Martín Villalba reviewed the different surface markers used historically for evaluating NK-cell activation and presented original results on NK-cell expression of different isoforms of the leukocyte receptor CD45 and correlation of these with their activation state.

3. Anne Marie Caminade reviewed the structure of dendrimers and presented the procedures for assessing their purity and possible degradation in different physical and chemical conditions, using equipment obtained thanks to this project. She also clarified practical question from participants regarding stability of the dendrimers in different storage conditions.

4. Miguel López-Botet summarized the preliminary results of a study of NK-cell receptor profiles in two cohorts of patients submitted by the Montpellier group: ones suffering Epstein-Barr virus reactivation in the context of post-transplant immunosuppression; and long-term survivals of different malignancies.

5. Alberto Anel presented an evaluation of the cytotoxic activityy exerted by NK cells expanded using different protocols (with/without cytokines and/or EBV+ cell lines).

6. Carlos Vilches listed previous results of his group that would not be recapitulated, and introduced the different topics that would be presented by group members and himself.

7. Elisa Cisneros showed an analysis of the distribution of KIR-gene haplotypes in Spaniards, as an example of a South European population. The results included the frequencies of common arrangements of the KIR complex, as well as of certain recombinants; many of these, characterized by the group, including a novel chimeric receptor combining domains of an inhibitory and an activating KIR.

Tuesday

1. Aura Muntasell presented her results on the effect of copy-number variation of the NKG2C gene on NK-cell phenotype (correlation with proportion of NKG2C+ cells and receptor density on the cell surface) and function (Ca2+ influx and proliferative response to cytokines and receptor crosslinking). She also presented a study correlating NK-cell phenotype and antibody-mediated NK-cell cytotoxicity (ADCC) against cytomegalovirus-infected fibroblasts.

2. Julián Pardo summarized an evaluation of cytotoxicity mediated by NK cells against cells from chronic lymphocytic leukemia patients, Key points of this study are proper existence of such activity, under-estimated in previous studies by other groups; and rough correlation between the degree of cytotoxicity and genetic disparity between effector and target cells according to the missing-self model, evaluated in collaboration with the Majadahonda group. Alternative strategies for a second, confirmatory set of experiments were discussed.

3. Elisa Cisneros presented a summary of polymorphism of the orphan KIR2DL5A receptor, the different phenotypes conferred by its alleles, and the experimental approach she is undertaking to identify the molecular mechanisms hidden underneath those phenotypes.

4. Carlos Vilches recapitulated historical contributions of the Majadahonda group to current knowledge on HLA-C molecules (whose expression controls much of NK-cell activity through recognition by multiple KIR), and presented a novel method developed in the laboratory to facilitate isolation of the whole HLA-C gene in an allele-specific manner. He also presented recent advances of the group in the search for ligands for KIR of unknown specificity.

5. Manuela Moraru presented original results on HSV-1 infection that reveal an epistatic interaction between a functional polymorphism in the CD16A molecule that mediates ADCC and a polymorphism of human IgG1. The two polymorphisms modulate affinity of the immunoglobulin for cellular and viral receptors for IgG. Preliminary results of ongoing functional studies are in support of the observed genetic interaction.

After general discussion of experimental approaches to address questions raised during the different talks, Alberto Anel reviewed the essential contributions achieved through networking within the CliNK project, presented an estimation of the timeframe for future Interreg-SUDOE calls and surveyed participants on their interest and proposals for possible participation in the next call. The idea was favorably received in general terms, and different possibilities were presented and discussed.

After closure of the meeting and lunch, several members of the consortium held smaller informal meetings to discuss the details of ongoing and future collaborations.

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