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Functions of open MHC class I molecule conformations
Vaníčková, Marie ; Poláková, Ingrid (advisor) ; Vaníková, Šárka (referee)
The major role of MHC class I molecules in adaptive system is to present antigen peptides derived from intracellular environment on the cell surface. These peptides are recognized by CD8+ T-lymphocytes and they can also interact with NK cells via trans-interaction. MHC class I molecules are composed of a heavy chain, β2-microglobulin (β2m, light chain) and peptide, forming a closed conformation. The heavy chain is non-covalently associated with the light chain and is folded into extracellular domain (α1, α2, α3 subunits), transmembrane domain and cytoplasmic domain (with conserved motifs). Upon active metabolism, the β2m and peptide may dissociate from the MHC I heavy chain what leads to the formation of open conformations of MHC I. This conformational change causes the subunit to unfold and allow its interaction with various receptors and molecules. Open conformers of MHC I may form cis-interactions with themselves creating homodimers involved in immunological functions or they can associate with different receptors on the cell surface creating heterodimers responsible for non-immunological functions. Soluble forms of free heavy chains also exist outside of the cell surface. Cis-associations are very important as they influence signaling pathways of the cell, inhibition or activation of...
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