témavezető: Gogolák Péter
helyszín (magyar oldal): Debreceni Egyetem helyszín rövidítés: DEÁOK
A kutatási téma leírása:
Tumour antigen specific cytotoxic T lymphocytes are definitely one of the main players of the antitumour immune response in the body. Their use in the tumour therapy would be unquestionable but problematic. The different alleles of the polymorphic MHC molecules can present tumour-associated or tumour-specific peptide antigens with different efficiency for specific T cell recognition. Because of the extreme polymorphism of the “classical” MHC molecules, the wide spread clinical use of tumour peptide epitope specific T cells is principally limited by either the phenomenon of MHC allotype restriction (T cells develop to recognise self MHC allotypes) or the detrimental effects of MHC alloreactions.
Non-polymorphic MHC molecules or MHC class Ib molecules play diverse role in the immune system. These molecules are virtually identical within different people of diverse genetic background. They can be categorised to different groups. Some of them can play different accessory roles in the process of the antigen presentation. Other groups have essential roles in the modulation of NK cell activation, anothers themselves are able to stabilize and present non-peptid antigens at the surface of different cell types. In this way non-peptide molecules can be also recognised by specific T cells.
CD1 molecules belonging to the group of MHC class Ib molecules are able to present lipid-like molecules. They can present microbial lipids and self-lipids to specific T cells. CD1c molecules were described to present lipid molecules which predominantly accumulated in leukaemia cells, so specific CD1c restricted T cells can mediate the killing of these transformed cells. Several malignant cell types – especially of white blood cell origin –express CD1c molecules, so these molecules can be regarded as targetable tumour markers. The non-polymorphic nature of these molecules renders them ideal therapeutic target for patients of different genetic background.
In the research we would like to describe lipid antigens associated with CD1c molecules within macrophage-like and cancer cell lines.
We would like to generate soluble CD1c molecules bound to specific lipids.
By the help of these CD1c molecule constructs, we would like to identify CD1c-lipid complex specific T cells in patients and healthy donors.
The successful work may provide further possibilities for the detailed structural investigation of different T cell receptor (TCR)-CD1c complexes which are rather poorly described so far. It can also raise the possibility to produce high affinity CD1c-lipid complex specific recombinant TCRs. Such TCR based bispecific reagents could discriminate between healthy and CD1c expressing cancer cells and subsequently re-direct the attack of the patients’ conventional T cells to them independently from the patients’ genetic background.
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