MHC class II invariant chains in antigen processing and presentation

Koch, Norbert; Lipp, Joachim; Pessara, Ulrich; Schenck, Klaus; Wraight, Christopher J.; Dobberstein, Bernhard

doi:10.1016/0968-0004(89)90013-3

Cited by 26 publications

(13 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Then, the translated proteins of Ii were detected by flow cytometry analysis, and the specificity of those antibodies was confirmed by immunoprecipitation. Polyacrylamide gel electrophoresis of the immunoprecipitated samples revealed the presence of the p33 and p41 isoforms of Ii, previously described on APCs (Strubin et al 1986;O'Sullivan et al 1987;Koch et al 1989), and the coassociated MHC class II molecules. The electrophoretic mobility of these proteins differs within cell types, suggesting differences in molecular weight.…”

Section: Discussionmentioning

confidence: 99%

Polarized Expression of CD74 by Gastric Epithelial Cells

Barrera

Beswick

Sierra

et al. 2005

J Histochem Cytochem.

View full text Add to dashboard Cite

S U M M A R Y CD74 is known as the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) that regulates the cell biology and functions of MHC class II molecules. Class II MHC and Ii expression was believed to be restricted to classical antigen-presenting cells (APC); however, during inflammation, other cell types, including mucosal epithelial cells, have also been reported to express class II MHC molecules. Given the importance of Ii in the biology of class II MHC, we sought to examine the expression of Ii by gastric epithelial cells (GEC) to determine whether class II MHC molecules in these nonconventional APC cells were under the control of Ii and to further support the role that these cells may play in local immune and inflammatory responses during Helicobacter pylori infection. Thus we examined the expression of Ii on GEC from human biopsy samples and then confirmed this observation using independent methods on several GEC lines. The mRNA for Ii was detected by RT-PCR, and the various protein isoforms were also detected. Interestingly, these cells have a high level expression of surface Ii, which is polarized to the apical surface. These studies are the first to demonstrate the constitutive expression of Ii by human GEC.

show abstract

Section: Discussionmentioning

confidence: 99%

Polarized Expression of CD74 by Gastric Epithelial Cells

Barrera

Beswick

Sierra

et al. 2005

J Histochem Cytochem.

View full text Add to dashboard Cite

show abstract

“…Because of alternative splicing, mice and humans also express p41 and p43, respectively Koch et al 1987;O'Sullivan et al 1987). The additional sequence in their exoplasmic domain has protease inhibitory ac-tivity especially to the cysteine protease cathepsin L (Koch et al 1989;Bevec et al 1996;Mihelič et al 2008) and influences the antigen-processing capacity of endosomes (Peterson and Miller 1992). In humans, but not in mice, an alternative start codon provides two additional Ii isoforms, p35 and p45, carrying a cytoplasmic extension that is shielded only after correct folding of the MHCII -Ii complex and, when exposed, serves as an ER-retention motif.…”

Section: Biosynthesis Of Mhciimentioning

confidence: 99%

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

Broeke

Wubbolts

Stoorvogel

2013

Cold Spring Harbor Perspectives in Biology

143

102

View full text Add to dashboard Cite

For the initiation of adaptive immune responses, dendritic cells present antigenic peptides in association with major histocompatibility complex class II (MHCII) to naïve CD4 þ T lymphocytes. In this review, we discuss how antigen presentation is regulated through intracellular processing and trafficking of MHCII. Newly synthesized MHCII is chaperoned by the invariant chain to endosomes, where peptides from endocytosed pathogens can bind. In nonactivated dendritic cells, peptide-loaded MHCII is ubiquitinated and consequently sorted by the ESCRT machinery to intraluminal vesicles of multivesicular bodies, ultimately leading to lysosomal degradation. Ubiquitination of newly synthesized MHCII is blocked when dendritic cells are activated, now allowing its transfer to the cell surface. This mode of regulation for MHCII is a prime example of how molecular processing and sorting at multivesicular bodies can determine the expression of signaling receptors at the plasma membrane.

show abstract

“…The high rate of class II synthesis gives immature DCs the possibility to charge a large number of class II molecules with immunogenic peptides. The concomitant abundant synthesis of Ii, which is also involved in antigen processing (22,26), would ensure that the peptide binding groove (35,36) of all de novo-synthesized class II molecules is protected until the class II/Ii complex reaches the organelle where it encounters the antigen, presumably the acidic endosome (11,12). The unusually high degree of I, sialylation in fresh LCs gives these polypeptides a strong negative charge.…”

Section: Biochemistry Of Class II and Ii Molecules Of Immaturementioning

confidence: 99%

Class II major histocompatibility complex molecules of murine dendritic cells: synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture.

Kämpgen

Koch

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

146

View full text Add to dashboard Cite

Dendritic cells (DCs), such as Langerhans cells (LCs) of the epidermis and the DCs of lymphoid organs such as spleen, are potent antigen presenting cells. DCs express high levels of major histocompatibility complex (MHC) class I molecules, but, partly because of the low numbers of primary DCs in any tissue, there has been no detailed study of the biochemistry of their class II molecules. This information may be needed to help explain recent findings that DCs process native protein antigens when freshly isolated from epidermis and spleen. Processing ceases during culture, yet a strong accessory function for activating resting T cells develops. We studied immunoprecipitatts of DC class II and invariant chain (1,) molecules by two-dimensional gel electrophoresis. We found that (i) freshly isolated LCs synthesize large amounts of class II and I, polypeptides; (ii) I; molecules that are known to be involved in antigen processing display an unusually large number of sialic acids in fresh LCs; (iii) with culture, class II and I, synthesis decreases dramatically and has virtually ceased at 3 days; and (iv) the turnover of class H in pulse/chase experiments is slow, being undetectable over a 12-to 32-hr culture period, whereas the turnover of I, is rapid. We conclude that MHC class H molecules of DCs do not seem to be qualitatively unique. However, the regulation of class II and Ii expression is distinctive in that biosynthesis proceeds vigorously for a short period of time and the newly synthesized class H remains stably on the cell surface, whereas Ii turns over rapidly. This may enable DCs to process and retain antigens in the peripheral tissues such as skin and migrate to the lymphoid organs to activate T cells there.Dendritic cells (DCs) represent a system of abundantly major histocompatibility complex (MHC) class II-expressing leukocytes. They occur in nonlymphoid organs, blood, afferent lymph, and lymphoid tissues (1). Two states ofdifferentiation can be distinguished (2, 3). "Immature" DCs, exemplified by freshly isolated epidermal Langerhans cells (LCs), are weak stimulators of resting T cells both in the allogeneic mixed leukocyte reaction (4,5) and in polyclonal responses such as oxidative mitogenesis, concanavalin A mitogenesis, and anti-CD3 mitogenesis (6). These fresh LCs (7, 8) as well as fresh DCs from spleen (9), however, are efficient in processing native protein antigens for MHC class II-restricted presentation to presensitized peptide-specific T cells (in vivo-primed T cells, clones, T-T hybridomas). Upon 1-3 days of culture in macrophage-or keratinocyte-conditioned medium, or in culture medium supplemented with granulocyte/macrophage colony-stimulating factor, their functional properties become inverted. "Mature" DCs lose the capacity to process exogenous antigens but at the same time acquire the ability to sensitize resting T cells (2, 3). The loss ofprocessing function is paralleled by the loss of acidic organelies such as endosomes (10), which are known as the compartments where class II e...

show abstract

MHC class II invariant chains in antigen processing and presentation

Cited by 26 publications

References 23 publications

Polarized Expression of CD74 by Gastric Epithelial Cells

Polarized Expression of CD74 by Gastric Epithelial Cells

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

Class II major histocompatibility complex molecules of murine dendritic cells: synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture.

Contact Info

Product

Resources

About