Antigen presentation by MHC class I
Antigen processing and presentation is the process by
which antigen-presenting cells express antigen on their cell
surface in a form recognizable by lymphocytes.
Antigen processing includes protein fragmentation
(proteolysis), association of the fragments with MHC (major histocompatibility complex),
and expression of the peptide-MHC complex at the cell surface where they can be
recognized by the T cell receptor
(TCR) on a T cell.
Expression of MHC molecules is constitutively activated during development in
professional antigen-presenting cells, such as B cells, dendritic cells and macrophages.
There are two classes of MHC proteins, MHC class I and MHC
class II.
MHC class I molecules are specialized for presentation of
endogenously synthesized proteins, including self-proteins and viral proteins synthesized
in host upon infection, to TCR of CD8+ T-cells.
Intracellular proteins are degraded into antigenic peptides by the 26S
proteasome and transported into endoplasmic reticulum (ER) via
TAP1 and TAP2 transporters.
MHC class I molecules are tethered to TAP transporter via
TAP-binding protein, Tapasin. MHC class
I heavy chains bind ER chaperone calnexin.
Upon folding, they dissociate from calnexin and bind
beta-2 microglobulin, ER chaperone
calreticulin and thiol oxodoreductase PDIA3.
Then, MHC class I proteins bind antigenic peptides.
MHC class I-peptide complex is transported to cell
surface for presentation to CD8+ T-cells [1]. MHC class
I heavy chains that fail to acquire a mature conformation in ER as a
result of defective folding or assembly with
Beta-2-microglobulin, are retranslocated via
Sec61 channel to cytosol for degradation by proteasome
[2].
References:
- Cresswell P, Ackerman AL, Giodini A, Peaper DR, Wearsch PA
Mechanisms of MHC class I-restricted antigen processing and cross-presentation.
Immunological reviews 2005 Oct;207:145-57
- Albring J, Koopmann JO, Hammerling GJ, Momburg F
Retrotranslocation of MHC class I heavy chain from the endoplasmic reticulum to the cytosol is dependent on ATP supply to the ER lumen.
Molecular immunology 2004 Jan;40(10):733-41
