Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Jan 9;27(1):1-5.
doi: 10.1038/sj.emboj.7601945. Epub 2007 Nov 29.

MHC class II molecules on the move for successful antigen presentation

Affiliations
Review

MHC class II molecules on the move for successful antigen presentation

Nuno Rocha et al. EMBO J. .

Abstract

Major histocompatibility complex class II (MHC II) molecules are targeted to endocytic compartments, known as MIIC, by the invariant chain (Ii) that is degraded upon arrival in these compartments. MHC II acquire antigenic fragments from endocytosed proteins for presentation at the cell surface. In a unique and complex series of reactions, MHC II succeed in exchanging a remaining fragment of Ii for other protein fragments in subdomains of MIIC before transport to the cell surface. Here, the mechanisms regulating loading and intracellular trafficking of MHC II are discussed.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The cell biology of antigen presentation by MHC II. MHC II αβ heterodimers are assembled in the endoplasmic reticulum (ER) and form a peptide-binding groove that is occupied by Ii. Ii chaperones MHC II often directly (route 1; black solid arrows) and sometimes indirectly after internalization from the cell surface (route 2; gray dashed arrows) into MIIC where Ii is degraded by a series of endosomal proteases with the CLIP fragment remaining (orange). HLA-DM assists exchange of CLIP for relevant exogenous antigenic fragments (red or yellow) in subdomains of MIIC (the internal vesicles) prior to transport for stable integration in the plasma membrane (blue arrows in MIIC) unless internalization is induced by processes like ubiquitination (Ub) of the MHC II β-chain cytoplasmic tail (route 3; pink dashed arrow).
Figure 2
Figure 2
Reciprocal coordination of motor proteins for bidirectional microtubule-based MIIC transport. Left: control of inward transport of MIIC toward the microtubule minus-end. Right: control of plus end-directed transport of MIIC to the cell periphery. Activation of Rab7 precedes formation of the tripartite Rab7-RILP-ORP1L complex. RILP interacts with the dynactin subunit p150Glued (a). Dynactin then interacts either with dynein (b(��)) or kinesin-2 (KIF3) (b(+)) motor proteins, specifying the direction of vesicle transport. Motor activity requires binding to a second LE membrane receptor, βIII spectrin (c(−)). Full activation of kinesin-2 may require a similar interaction with a general receptor on MIIC (c(+)). In this model, the p150Glued-associated type of motor specifies the direction of MIIC transport (d).

Similar articles

Cited by

References

    1. Bakke O, Dobberstein B (1990) MHC class II-associated invariant chain contains a sorting signal for endosomal compartments. Cell 63: 707–716 - PubMed
    1. Bikoff EK, Huang LY, Episkopou V, van Meerwijk J, Germain RN, Robertson EJ (1993) Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression. J Exp Med 177: 1699–1712 - PMC - PubMed
    1. Blander JM, Medzhitov R (2006) Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 440: 808–812 - PubMed
    1. Boes M, Cerny J, Massol R, Op den Brouw M, Kirchhausen T, Chen J, Ploegh HL (2002) T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418: 983–988 - PubMed
    1. Brown CL, Maier KC, Stauber T, Ginkel LM, Wordeman L, Vernos I, Schroer TA (2005) Kinesin-2 is a motor for late endosomes and lysosomes. Traffic 6: 1114–1124 - PubMed

MeSH terms

Substances