Loading of antigenic peptides on to class I MHC

Stable Identifier
R-HSA-8951499
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

MHC class I heterodimers are only stable in peptide bound form and only as a trimer (with bound peptide) present on the cell surface. Class I MHC molecules prefer nonapeptides, and less frequently use octa- or deca-peptides. The peptide binding groove in MHC class I molecules is formed by the intimate association of the alpha1 and alpha2 domains of the heavy chain. Structural studies have revealed that the alpha1:alpha2 domains form a single peptide binding groove consisting of 2 parallel helices on a floor of 8 beta-strands. Hydrogen bonding networks are established in the binding groove with the antigenic peptide main chain and terminal atoms that enable largely sequence independent ligation. Upon peptide binding the class I MHC molecule releases from the peptide loading complex (PLC) and clusters at ER exit sites and is finally exported to the cell surface.
MHC I molecules bound to low-affinity peptides are not transferred to the cell surface and are instead cycled back to ER. They can proceed to the cell surface only when they become bound to high-affinity peptide (Howe et al, 2009; Garstka et al, 2007). Calreticulin binds to these low-affinity peptide bound class I molecules and mediate the retrieval from golgi apparatus to ER and for effcient presentation of a model antigen (Howe et al, 2009).

Literature References
PubMed ID Title Journal Year
19851281 Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class I molecules

Howe, C, Garstka, M, Al-Balushi, M, Ghanem, E, Antoniou, AN, Fritzsche, S, Jankevicius, G, Kontouli, N, Schneeweiss, C, Williams, A, Elliott, T, Springer, S

EMBO J 2009
2038058 Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution

Saper, MA, Bjorkman, PJ, Wiley, DC

J Mol Biol 1991
17656363 Peptide-receptive major histocompatibility complex class I molecules cycle between endoplasmic reticulum and cis-Golgi in wild-type lymphocytes

Garstka, M, Borchert, B, Al-Balushi, M, Praveen, PV, Kühl, N, Majoul, I, Duden, R, Springer, S

J Biol Chem 2007
16473882 Structural definition of the H-2Kd peptide-binding motif

Mitaksov, V, Fremont, DH

J Biol Chem 2006
21050182 The cell biology of major histocompatibility complex class I assembly: towards a molecular understanding

Van Hateren, A, James, E, Bailey, A, Phillips, A, Dalchau, N, Elliott, T

Tissue Antigens 2010
Participants
Participant Of
Orthologous Events
Authored
Reviewed
Created