Reactome | Loading of antigenic peptides on to class I MHC

Loading of antigenic peptides on to class I MHC

Stable Identifier

R-HSA-8951499

Type

Reaction [binding]

Species

Homo sapiens

Compartment

integral component of lumenal side of endoplasmic reticulum membrane, endoplasmic reticulum lumen, endoplasmic reticulum membrane

ReviewStatus

5/5

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Loading of antigenic peptides on to class I MHC

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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
2038058	Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution Wiley, DC, Bjorkman, PJ, Saper, MA	J Mol Biol	1991
19851281	Calreticulin-dependent recycling in the early secretory pathway mediates optimal peptide loading of MHC class I molecules Fritzsche, S, Kontouli, N, Williams, A, Ghanem, E, Jankevicius, G, Elliott, T, Springer, S, Garstka, M, Al-Balushi, M, Schneeweiss, C, Howe, C, Antoniou, AN	EMBO J	2009
17656363	Peptide-receptive major histocompatibility complex class I molecules cycle between endoplasmic reticulum and cis-Golgi in wild-type lymphocytes Duden, R, Majoul, I, Borchert, B, Springer, S, Kühl, N, Garstka, M, Al-Balushi, M, Praveen, PV	J Biol Chem	2007
16473882	Structural definition of the H-2Kd peptide-binding motif Fremont, DH, Mitaksov, V	J Biol Chem	2006
21050182	The cell biology of major histocompatibility complex class I assembly: towards a molecular understanding Van Hateren, A, Dalchau, N, Bailey, A, Elliott, T, Phillips, A, James, E	Tissue Antigens	2010