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CURATOR
A pinboard by
Paula Ruibal

PhD Student, Heinrich Pette Institute

PINBOARD SUMMARY

I focus on the importance of HLA and TCR diversity during EVD and in the outcome to the disease.

The HLA class I and II genes play a very important role in the initiation of the adaptive immune responses. These molecules expressed on the surface of antigen presenting cells are highly polymorphic in order to present a wide array of antigenic peptides and different levels of this diversity as well as the expression of specific alleles have been associated to improved immune responses to viral infections. Facing the HLA-peptide complex during the immunological synapse, the CDR3 sequence in the T cell receptor (TCR) determines antigen specificity of the T cell responses. In order to be able to recognize the infinite possibility of peptides presented, the TCR display a highly diverse repertoire which can also be correlated to an improved capacity of the host to clear viral infections. In this study we genotyped the HLA class I and II alleles from fatal cases and survivors in order to evaluate the potential influence of these alleles polymorphism in disease outcome. Heterozygosity at the HLA-A locus was significantly associated with survival supporting the important role of CD8 T cell responses during EVD disease. We also sequenced the TCR of Ebola virus disease (EVD) patients who succumbed or survived the disease and evaluated the possible influence of the TCR repertoire diversity in the clearance of Ebola virus (EBOV) and in recovery. Our results indicated that survival is significantly associated with an elevated TCR diversity as well as with a lower amount of shared TCR sequences between individuals. Our findings support the importance of HLA and TCR polymorphisms for the activation of a broad and effective adaptive immune response.

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