Objective
The histocompatibility antigens play a crutial role in normal and pathological immune processes. There are two classes of the antigens. The class I is expressed by every cell and present the endogen peptides. to immune cells for eliminate malignant or infected cells. The class II antigens serve for presentation of processed exogen peptides and is expressed in restricted number of cells - antigen presenting cells. Both classes are coded by several gens, which cluster in two regions, according to their functions. This two clusters are divided by only one megabase gap and however have different patterns of expression: while class I is ubiquitous, class II is expressed by particular cell at particular developmental stage.
There are some examples of multilevel regulation by chromatine conformation of gens clusters in man, beta-globin claster is the better known. Chromatin folding and unfolding accomplished during cell development is the mechanism of "opening" or "shut douw" of expression, and precede its initiation. The changes in chromatin conformation are regulated by locus control region, already described in several human clasters, but not in the class I or II region.
Taking in account the pathology, followed by complete absence of class II expression we proposed to study the process of normal and pathological inactivation of class II gens in several molecular models.
The knowledge of class II regulation at the chromatin level will promote our comprehension of bare lymphocyte syndrom and autoimmunity, will also fernish new approach of improvement of immune response against infection.
We propose also a new and simple method to test the locus control region capacity, which can be applied in any situation, when gen transfection is needed.
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Programme(s)
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Coordinator
75006 PARIS
France
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