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IMMUNEDIVERSITY

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Defining of human adaptive immune gene diversity and its impact on disease

Why do vaccines protect some people but not all? Why can some people develop potent neutralizing antibodies to infections, while others cannot? Why do some people develop immune-associated diseases such as allergy, rheumatoid arth... ver más

30/11/2024

3M€

Presupuesto del proyecto: 3M€

Líder del proyecto

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2024-11-30

ERC-2017-ADG: ERC Advanced Grant

I+D

Cerrada hace 7 años

0% 100% 100%

2 Participantes

2.50M€ | Lider

SUMIVENT

198.95K€ | Participante

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Duración del proyecto: 77 meses Fecha Inicio: 2018-06-18
Fecha Fin: 2024-11-30

Líder del proyecto

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 3M€

Descripción del proyecto Why do vaccines protect some people but not all? Why can some people develop potent neutralizing antibodies to infections, while others cannot? Why do some people develop immune-associated diseases such as allergy, rheumatoid arthritis, multiple sclerosis and diabetes over their lifetimes, when the body has evolved to tolerate self? The answer lies in the adaptive immune system. B and T lymphocytes of the adaptive system express highly polymorphic receptors that allow for the recognition of large numbers of antigens. Our research is now uncovering an enormous heterogeneity in the germline genes that encode our B and T cell receptors. This fact has not been well appreciated because of the high complexity of the genomic regions that encode these receptors, with the presence of large insertions and deletions, a high degree of repetitiveness and gene copy number variations, which cannot be adequately met with conventional whole genome sequencing approaches. We have developed a state-of-the-art approach we call IgDiscover, which comprises novel molecular library preparation approaches, next generation immune repertoire sequencing, computational analysis and a software that allows rapid construction of personalized antibody gene databases encompassing the hundreds of germline gene segments that rearrange to make up each individual’s naïve B cell repertoire. Thus, IgDiscover offers new possibilities to define human genetic diversity in these loci. This proposal also describes our development of ImmuneDiscover, a high throughput approach enabling personalized immune-profiling of very large numbers of individuals (>1000), encompassing not only Ig genes but also T cell receptor genes and the genes encoding the human major histocompatibility complexes. Here, we will use IgDiscover and ImmuneDiscover to elucidate global diversity in adaptive immune genes and we will investigate potential associations between antibody germline genes and the development of rheumatoid arthritis.

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