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(in Russian) |
Themes developed in the laboratory:
1. "Molecular and cellular mechanisms of induction of different subclasses
of T lymphocytes and their interaction with the epitopes of histocompatibility molecules."
(2005-2008) The theme is developed according to the plan of RAMS and aimed on the study of
the role of specific and nonspecific cognate interactions between T lymphocyte and APC in
induction of different functional subclasses of T lymphocytes.
2. "Intrathymic selection and immunotherapy of cancer: development of
TCR-transgenic model."
In general, inefficiency of anti-tumor vaccines targeted to tumor-associated antigens
is result of thymic negative selection of T cells with high avidity to these antigens.
So, to be effective, new generation of cancer vaccines should operate in thymus
by prevention of deletion of T cells with corresponding specificity. To develop
new approach to design and evaluation of these vaccines, we'll make transgenic
mice with MHC class I specific TCR, cloned in our laboratory from CD8+
memory T cells specific to Kb molecule of thymoma EL4 cells. These TCR
transgenic mice would be useful mean to make visible negative selection of
self-reactive T cells in different Kb-mutants and search for agents
capable to influence intrathymic selection. We will investigate the ability of
selected T cells to protect mice from tumor growth. Overall goal of the study
is to establish a potential system for correct search and testing of cancer vaccines.
3. "Molecular and cellular mechanisms of peripheral selection of T lymphocytes
and their interaction with the epitopes of histocompatibility molecules."
The grant of Russion Foundation for Basic Research (RFBR) N-05-04-49793a (2005-2007).
This theme is devoted to investigation of immunoregulatory functions of unusual
subpopulation of APC with combining properties of professional APCs (CD80+)
and activated neutrophils (Gr-1+CD31-). This subpopulation
differentiates in primary, but not secondary response on allogeneic tumor cells.
4. "Mechanisms of selection of autoimmune T cells."
The grant of RFBR N-04-04-49187a (2004-2006). Principal investigators:
L.M.Khromykh and L.A.Pobezinsky. Works on this project are aimed on investigation
of T lymphocytes with TCRs specific to MHC class I and syngeneic MHC class II
molecules simultaneously. Mechanisma of their selection are investigated by means
of molecular cloning of alpha- and beta chains of TCRs and obtaining transgenic animals.
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