Invariant chain

McCabe Jr., M.J., Dias, J.A. and Lawrence, D.A., Lead influences translational or post-translational regulation of la expression and increases invariant chain expression in mouse B cells. J. Biochem. Toxicol., 6, 269, 1991. 

Castellino F. 1997. Antigen presentation by MHC Class II molecules Invariant chain function, protein trafficking and the molecular basis of diverse determinant capture. Hum Immunol. 54 159-169. 

The earliest attempts at model analysis of polysaccharides -typified by the x-ray crystal structure analysis of amylose triacetate - were usually conducted in three steps ( L). In the first step, a model of the chain was established which was in agreement with the fiber repeat and the lattice geometry, as obtained from diffraction data. In the second step, the invariant chain model was packed into the unit cell, subject to constraints imposed by nonbonded contacts. This was followed, in the third step, by efforts to reconcile calculated and observed structure factor amplitudes. It was quickly realized that helical models of polysaccharide chains could be easily generated and varied using the virtual bond method. Figure 1 illustrates the generation of a two-fold helical model of a (l- U)-linked polysaccharide chain. 

SMA SSEA-I smooth muscle actin stage-specific embryonic antigen characterized as a glycosphingolipid similar to Ii (MHC invariant chain)... 

P6. Pierre, P., and Mellman, I., Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell 93(7), 1135-1145 (1998). 

Fig. 14.5 The TCR Complex is associated with a number of T< ll specific membrane-spanning proteins.31 The antigen receptors and the co-receptors, CDS, CD4, and CDS, together with associated enzymes, tyrosine kinases and phosphatases, form the actual signalling complex. The cytoplasmic chains of the co-receptor molecules have characteristic consensus sequences, the ITAMs (immunoreceptor tyrosine activation motife). Each of the invariant -chains and the CD3-y,8, e chains, contain 1-3 copies of the RAM motife. The structure of the TCR-signalling complex still needs to be clarified.

CLIP MHC-class Il-associated invariant chain peptide... 

CLIP Class 11-associated invariant chain (li) peptide... 

Invariant chain Monocarboxylate transporter MHC class I MHC class II Na/KATPase Neuropilin 1 (Receptor)... 

Theorem C.6 establishes that the dynamical system generated by the vector field (C.l) on K", restricted to the limit set L, is topologically equivalent to the dynamical system generated by a Lipschitz vector field on ZZ restricted to Q L). As a consequence, these two dynamical systems share common dynamical properties. Since Z, is a compact invariant set, so too is Q L) a compact invariant set. It is also known that limit sets are chain-recurrent (see [C] for the definition) and so Q(L) has this property as well. Therefore, the dynamics on L are that of a compact, invariant, chain-recurrent set in one less dimension. 

Further, there is some evidence that posttranslationally modified peptides may be recognized (Shawar et at., 1990 Pfeffer et al., 1992) and the invariant chain which associates with MHC class II before peptide recognition can be variously glycosylated (Sant et al., 1985 Steward et al., 1990). 

Invariant chain is a transmembrane protein which temporarily associates in the ER and the Golgi apparatus with class II gene products of the major histocompatibility complex. A small portion of the invariant chain molecules carry a chondroitin sulfate chain [186]. The proteoglycan form of the invariant chain was shown to play a role in the stimulation ofT cell response [187]. 

MHC class I molecules are folded by support of a variety of chaperones, e.g., calnexin, calreticulin, tapasin. The class II pathway has to exclude the presentation of peptides of intracellular origin. Therefore, in the ER MHC class II molecules remain associated with the invariant chain Ii, where the CLIP region of Ii occupies the peptide-binding cleft [27]. CLIP is removed from the MHC in the MHC class II compartment MIIC [28], MHC class II molecules adopt a conformational change upon loading with peptides that allows the sorting to the cell surface. 

Cresswell P (1992) Chemistry and functional role of the invariant chain, Curr Opin Immunol 4 87-92. 

Sherman MA, Weber DA. Jensen PE (1995) DM enhances peplide binding to class II MHC by release of invariant chain-derived peptide, Immunity 3 197-205. 

Mechterscheimer G, Staudter M, Majdie O. Expression of HLA-A, B, C, beta-microglobulin, HLA-DR, -DP, -DQ, and HLA-D-associated invariant chain in soft tissue tumors. Int J Cancer. 1990 46 813-823. 

Arunachalam, B., and Cresswell, P. (1995). Molecular requirements for the interaction of class II major histocompatibility complex and invariant chain with calnexin. J. Biol. Chem. 270, 2784-2790. 

Romagnoli, P., and Germain, R. (1995). Inhibition of invariant chain (li)-calnexin interaction results in enhanced degradation of li but does not prevent the assembly of alfa beta li complexes. J. Exp. Med. 182, 2027-2036. 

The CD74 (anti-MHG 11 invariant chain) mAb LLl conjugated to various Auger elec-... 

Perkins, J. D., Munn, S. R., Barr, D., Ferguson, D. C., and Carpenter, H. A. Evidence that the soluble interleukin-2 receptor level may determine the optimal time for cystoscopically-di-rected biopsy in pancreaticoduodenal allograft recipients. Transplantation 49,363-366 (1990). Pessara, U., and Koch, N. Tumor necrosis factor alpha regulates expression of the major histocompatibility complex class 11-associated invariant chain by binding of an NF-kappa B-like factor to a promoter element. Mol. Cell Biol. 10, 4146-4154 (1990). 

Momburg F, Fuchs S, Drexler J, et al. (1993). Epitope-specific enhancement of antigen presentation by invariant chain. /. Exp. Med. 178 1453-1458. 

Fig. 1. The MHC class II antigen presentation pathway. MHC class II proteins (DR-ot and DR-P) are inserted into the ER membrane and assemble with the invariant chain (li). li blocks the peptide binding groove of DR-ot/p. These complexes are transported to the Golgi apparatus and then directed to TGN/ endosomes by li. There is proteolysis of li, and DR oi/p CLIP complexes arrive in the MIIC. Antigenic proteins are taken up by endocytosis or phagocytosis into endosomes and degraded into peptides, which are also delivered to the MIIC. Peptides are loaded onto DR-oe/p complexes by the action of DM, which binds to class II complexes and exchanges peptides for CLIP. Peptide-loaded class II complexes are transported to the cell surface for recognition by T cell receptors of CD4" T lymphocytes...

Cresswell P (1996) Invariant chain structure and MHC class II function. Cell 84 505-507 Cunningham AL, Turner RR, Miller AC, Para MF, Merigan TC (1985) Evolution of recurrent herpes simplex virus lesions an immunohistologic study. J Clin Invest 75 226-295 Denzin LK, Cresswell P (1995) HLA-DM induces CLIP dissociation from MHC class II a/(3 dimers and facilitates peptide loading. Cell 82 155 165... 

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