Diversity in MHC class II antigen presentation

Robinson, John H.; Delvig, Alexei A.

doi:10.1046/j.0019-2805.2001.01358.x

Cited by 89 publications

(90 citation statements)

References 131 publications

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“…We, 26,59 and others (reviewed in ref. 60), have previously shown that the intracellular origin of the MHC class II molecules used to form peptide-MHC complexes can profoundly influence subsequent CD4 + T cell activation. Therefore we compared the intracellular origins of the MHC class II molecules in aggrecan-specific B cells, macrophages and DC that were involved in the presentation of the p84-103 epitope.…”

Section: Discussionmentioning

confidence: 99%

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4⁺ T helper type 1 subset differentiation

Hine

Pradipta

et al. 2012

Immunology

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Summary Effective immune responses require antigen uptake by antigen‐presenting cells (APC), followed by controlled endocytic proteolysis resulting in the generation of antigen‐derived peptide fragments that associate with intracellular MHC class II molecules. The resultant peptide–MHC class II complexes then move to the APC surface where they activate CD4+ T cells. Dendritic cells (DC), macrophages and B cells act as efficient APC. In many settings, including the T helper type 1 (Th1) ‐dependent, proteoglycan‐induced arthritis model of rheumatoid arthritis, accumulating evidence demonstrates that antigen presentation by B cells is required for optimal CD4+ T cell activation. The reasons behind this however, remain unclear. In this study we have compared the activation of CD4+ T cells specific for the proteoglycan aggrecan following antigen presentation by DC, macrophages and B cells. We show that aggrecan‐specific B cells are equally efficient APC as DC and macrophages and use similar intracellular antigen‐processing pathways. Importantly, we also show that antigen presentation by aggrecan‐specific B cells to TCR transgenic CD4+ T cells results in enhanced CD4+ T cell interferon‐γ production and Th1 effector sub‐set differentiation compared with that seen with DC. We conclude that preferential CD4+ Th1 differentiation may define the requirement for B cell APC function in both proteoglycan‐induced arthritis and rheumatoid arthritis.

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Section: Discussionmentioning

confidence: 99%

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4⁺ T helper type 1 subset differentiation

Hine

Pradipta

et al. 2012

Immunology

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“…Role of Endosome Acidification in Antigen Presentation of rPA-Progress of endocytosed antigens from early endosomes to the low pH environment of late endosomes or lysosomes is required for presentation of many (17) but not all (24,42,43) CD4 ϩ T-cell epitopes. Macrophages were treated with NH 4 Cl, a weak base that raises endosomal pH (44) to determine whether a low pH is required for presentation of each of the PA epitopes.…”

Section: Kinetics Of Presentation Of Pa Epitopes By Macrophages-mentioning

confidence: 99%

“…ϩ T-cells are liberated from protein antigens following some form of antigen processing before they are accessible to bind MHC class II molecules usually in acidic endocytic compartments of antigen presenting cells (APC) such as macrophages, dendritic cells, and B cells (17)(18)(19)(20)(21)(22)(23)(24). Following uptake by APC, processing is thought to be initiated during transport through the endosomal system by unfolding of antigens induced by low pH (25,26), oxidation (27), disulphide reduction (28 -30), or limited cleavage by lysosomal enzymes such as asparaginyl endopeptidase (31).…”

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confidence: 99%

“…Peptide epitopes liberated during processing usually bind newly synthesized MHC class II molecules optimally at low pH under the control of chaperones DM and DO following degradation of the invariant chain. Alternatively, epitopes in structurally flexible regions of protein antigens may bind mature MHC class II recycled from the APC surface in neutral or mildly acidic endosomal compartments (24,37). Further processing or "trimming" of exposed amino acids of the peptides already bound to MHC molecules can occur (38), mediated by enzymes such as the metalloproteinase aminopeptidase N (39).…”

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Differential Processing of CD4 T-cell Epitopes from the Protective Antigen of Bacillus anthracis

Musson

Walker

Flick-Smith

et al. 2003

Journal of Biological Chemistry

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We have mapped CD4؉ T-cell epitopes located in three domains of the recombinant protective antigen of Bacillus anthracis. Mouse T-cell hybridomas specific for these epitopes were generated to study the mechanisms of proteolytic processing of recombinant protective antigen for antigen presentation by bone marrow-derived macrophages. Overall, epitopes differed considerably in their processing requirements. In particular, the kinetics of presentation, ranging from 15 (fast) to 120 min (slow), suggested sequential liberation of epitopes during proteolytic processing of the intact PA molecule. Pretreatment of macrophages with ammonium chloride or inhibitors of the major enzyme families showed that T-cell responses to an epitope presented with fast kinetics were unaffected by raising endosomal pH or inhibiting cysteine or aspartic proteinases, suggesting presentation independent of lysosomal processing. In contrast, responses to epitopes presented with slower kinetics were dependent on low pH and the activity of cysteine or aspartic proteinases indicating a requirement for lysosomal processing. In addition, responses to all epitopes, whether their presentation was dependent on low pH or not, were prevented by treatment of macrophages with broad spectrum serine proteinase inhibitors. Thus, our data are consistent with a model of sequential antigen processing within the endosomal system, beginning with a pre-processing step mediated by serine or metalloproteinases prior to further processing by lysosomal enzymes. Rapidly presented epitopes seemed to require only limited proteolysis at earlier stages of endocytosis, whereas the majority of epitopes required more extensive processing by neutral proteinases followed by lysosomal enzymes.

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“…It is increasingly apparent from studies using pathogenderived antigens that use of the recycling MHC class II pathway may be more prevalent than originally predicted (reviewed in [27]). It is therefore likely that our finding may have wider implications for antigen presentation.…”

Section: A Model For Enhanced Presentation Of Certain T Cell Epitopesmentioning

confidence: 99%

Lowering the affinity between antigen and the B cell receptor can enhance antigen presentation

Brooks

Knight

2004

Eur J Immunol

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The B cell receptor (BCR) enables antigen-specific B cells to bind, internalize and target antigens for processing into small peptide fragments. These epitopes are then expressed on the plasma membrane in association with MHC class II molecules for recognition by CD4 + T cells. The affinity of the interaction between the BCR and antigen plays an important part in determining T cell epitope generation. In this report we provide evidence that the efficiency of antigen presentation by specific B cells does not need to be directly proportional to antigen/BCR affinity. We show that increased presentation can result from lowering the affinity of the antigen/BCR interaction. This finding suggests a novel mechanism by which B cells can recruit T cell help and obtain survival signals. Activation of these cells may have consequences for the generation of the B cell repertoire.

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Diversity in MHC class II antigen presentation

Cited by 89 publications

References 131 publications

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4⁺ T helper type 1 subset differentiation

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4⁺ T helper type 1 subset differentiation

Differential Processing of CD4 T-cell Epitopes from the Protective Antigen of Bacillus anthracis

Lowering the affinity between antigen and the B cell receptor can enhance antigen presentation

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Diversity in MHC class II antigen presentation

Cited by 89 publications

References 131 publications

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4+ T helper type 1 subset differentiation

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4+ T helper type 1 subset differentiation

Differential Processing of CD4 T-cell Epitopes from the Protective Antigen of Bacillus anthracis

Lowering the affinity between antigen and the B cell receptor can enhance antigen presentation

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Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4⁺ T helper type 1 subset differentiation

Presentation of the candidate rheumatoid arthritis autoantigen aggrecan by antigen‐specific B cells induces enhanced CD4⁺ T helper type 1 subset differentiation