Intracellular assembly and transport of endogenous peptide-MHC class II complexes

Rudensky, Alexander Y.; Marić, Maja; Eastman, Susan; Shoemaker, Lee; deRoos, Paul; Blum, Janice S.

doi:10.1016/1074-7613(94)90048-5

Cited by 110 publications

(69 citation statements)

References 33 publications

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“…The formation of HEL 46 -61 -I-A k peptide-class II complexes recognized by both C4H3 mAb and TCR transgenic 3A9 T cells requires the invariant chain and the neosynthesis of CII molecules (17). Moreover, HEL processing involves an acidic compartment related to late endosome or the MIIC (18).…”

Section: Discussionmentioning

confidence: 99%

“…BCRtargeted Ags access the endocytic compartments very efficiently, and this property contributes to their enhanced processing and presentation compared with uptake of fluid phase-added Ag. The processing of HEL involves the generation of HEL 46 -61 -I-A k complexes in late endosomal compartments (17,18). Both 3A9 T cells and the C4H3 mAb recognize the peptide-MHC complex (16,31).…”

Section: Discussionmentioning

confidence: 99%

“…T cells from 3A9 mice recognize the same epitope as C4H3, i.e., HEL 46 -61 -I-A k (11,13). This epitope is buried within HEL, and therefore must be processed in late endosomal compartments (17,18). This is expected to occur in compartments that are accessed by both fluid phase and BCR uptake of HEL.…”

Section: Differential Effect Of Ligation Of Type I and Ii Complexes Fmentioning

confidence: 99%

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The Pathway of Antigen Uptake and Processing Dictates MHC Class II-Mediated B Cell Survival and Activation

Nashar

Drake

2005

The Journal of Immunology

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The influence of the pathway of Ag uptake and processing on MHC class II (CII)-mediated B cell function is unknown. In this study, we investigate in resting and activated (via the BCR or CD40) B cells the biological properties of CII-peptide complexes (CII-peptide) generated by either the BCR-mediated Ag processing (type I complex) or fluid phase Ag processing (type II complex). Compared with type I complex, ligation of type II complex by either specific Ab or the TCR in Ag-presenting assay results in significant decreases in B cell survival rate (50–100%) and expression levels of CII, CD86, and CD54. Loss of B cells following ligation of type II complex occurs in the presence of a comparatively good level of specific CD4+ T cell division, indicating that B cell loss is a late event following T cell stimulation. Comparative analysis of T and B cell conjugates after Ab ligation of type I or II complex reveals decreased efficiency of the latter in forming conjugates. Neither initial differential levels of CII and other studied surface markers, B cell type inherent differences, BCR signaling, T cell proliferation, nor initial density of CII-peptide complexes could explain the T cell-induced B cell loss. We propose that the context in which CII-peptide complexes are present in the membrane following BCR uptake and processing leads to B cell survival. Thus, appropriate targeting of Ag ensures generation of relevant immune responses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Differential Effect Of Ligation Of Type I and Ii Complexes Fmentioning

confidence: 99%

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The Pathway of Antigen Uptake and Processing Dictates MHC Class II-Mediated B Cell Survival and Activation

Nashar

Drake

2005

The Journal of Immunology

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“…These structures were termed the MHC class II compartment or MIIC. Using different experimental approaches, several groups went on to identify MIIC as a site where peptide±MHC-II complexes are formed (Harding and Geuze, 1993;Qiu et al, 1994;Rudensky et al, 1994;Tulp et al, 1994;West et al, 1994). Detailed analysis of human and mouse cells have suggested that the MIIC may be a conventional late endocytic compartment found in many cell types, but is specialized in APCs to contain Ag-processing molecules (Kleijmeer et al, 1997;Geuze, 1998).…”

Section: Mhc-ii Ag Processing and Presentationmentioning

confidence: 99%

Phagocytic processing of antigens for presentation by class II major histocompatibility complex molecules

1999

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Microbes and other particulate antigens (Ags) are internalized by phagocytosis and then reside in plasma membrane‐derived phagosomes. The contribution of phagosomes to the degradation of Ags has long been appreciated. It has been unclear, however, whether peptides derived from these degraded antigens bind class II major histocompatibility complex (MHC‐II) molecules within phagosomes or within endocytic compartments that receive Ag fragments from phagosomes. Recent experiments have demonstrated that phagosomes containing Ag‐ conjugated latex beads express a full complement of Ag‐processing molecules, e.g. MHC‐II molecules, invariant chain, H2‐DM and proteases sufficient to degrade bead‐ associated Ag. These phagosomes mediate the formation of peptide–MHC‐II complexes, which are transported to the cell surface and presented to T cells. Phagosomes acquire both newly synthesized and plasma membrane‐derived MHC‐II molecules, but the formation of peptide–MHC‐II complexes in phagosomes primarily involves newly synthesized MHC‐II molecules. The content and traffic of phagosomal proteins vary considerably with the type of Ag ingested. Pathogenic microbes can alter phagosome composition and function to reduce Ag processing. For example, Mycobacterium tuberculosis blocks the maturation of phagosomes and reduces the ability of infected cells to present exogenous soluble protein Ags.

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“…Protein Ags must be internalized into acidic endosomal and lysosomal compartments for processing to yield the short peptides of 12-25 aa that optimally bind MHC class II proteins (1)(2)(3)(4). These peptides generated within APC can intersect and bind class II proteins throughout the endosomal pathway (5)(6)(7)(8)(9). However, peptide association with newly synthesized class II molecules may be most favored in the late endosomal/ prelysosomal compartment termed MIIC (6, 7, 9 -11).…”

mentioning

confidence: 99%

Cysteinylation of MHC Class II Ligands: Peptide Endocytosis and Reduction Within APC Influences T Cell Recognition

Haque

Hawes

Blum

2001

The Journal of Immunology

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124

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Peptides bind cell surface MHC class II proteins to yield complexes capable of activating CD4+ T cells. By contrast, protein Ags require internalization and processing by APC before functional presentation. Here, T cell recognition of a short peptide in the context of class II proteins occurred only after delivery of this ligand to mature endosomal/lysosomal compartments within APC. Functional and biochemical studies revealed that a central cysteine within the peptide was cysteinylated, perturbing T cell recognition of this epitope. Internalization and processing of the modified epitope by APC, was required to restore T cell recognition. Peptide cysteinylation and reduction could occur rapidly and reversibly before MHC binding. Cysteinylation did not disrupt peptide binding to class II molecules, rather the modified peptide displayed an enhanced affinity for MHC at neutral pH. However, once the peptide was bound to class II proteins, oxidation or reduction of cysteine residues was severely limited. Cysteinylation has been shown to radically influence T cell responses to MHC class I ligands. The ability of professional APC to reductively cleave this peptide modification presumably evolved to circumvent a similar problem in MHC class II ligand recognition.

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Intracellular assembly and transport of endogenous peptide-MHC class II complexes

Cited by 110 publications

References 33 publications

The Pathway of Antigen Uptake and Processing Dictates MHC Class II-Mediated B Cell Survival and Activation

The Pathway of Antigen Uptake and Processing Dictates MHC Class II-Mediated B Cell Survival and Activation

Phagocytic processing of antigens for presentation by class II major histocompatibility complex molecules

Cysteinylation of MHC Class II Ligands: Peptide Endocytosis and Reduction Within APC Influences T Cell Recognition

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