Differential MHC class II presentation of a pathogenic autoantigen during health and disease

The Journal of Immunology : Official Journal of the American Association of Immunologists
Fei F ShihPaul M Allen

Abstract

Glucose-6-phosphate isomerase (GPI) is the target autoantigen recognized by KRN T cells in the K/BxN model of rheumatoid arthritis. T cell reactivity to this ubiquitous Ag results in the recruitment of anti-GPI B cells and subsequent immune complex-mediated arthritis. Because all APCs have the capacity to process and present this autoantigen, it is unclear why systemic autoimmunity with polyclonal B cell activation does not ensue. To this end, we examined how GPI is presented by B cells relative to other immunologically relevant APCs such as dendritic cells (DCs) and macrophages in the steady state, during different phases of arthritis development, and after TLR stimulation. Although all APCs can process and present the GPI:I-A(g7) complex, they do so with different efficiencies. DCs are the most potent at baseline and become progressively more potent with disease development correlating with immune complex uptake. Interestingly, in vivo and in vitro maturation of DCs did not enhance GPI presentation, suggesting that DCs use mechanisms to regulate the presentation of self-peptides. Non-GPI-specific B cells are the weakest APCs (100-fold less potent than DCs) and fail to productively engage KRN T cells at steady state and during...Continue Reading

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Citations

Nov 28, 2008·Arthritis and Rheumatism·Kristen MonteFei F Shih
Feb 10, 2010·Nature Reviews. Rheumatology·Argyrios N TheofilopoulosRoberto Baccala
Mar 21, 2012·Autoimmunity·David LuckeyVeena Taneja
Feb 2, 2013·American Journal of Respiratory Cell and Molecular Biology·Rebecca A ShillingHaochu Huang
Jul 8, 2009·Immunology and Cell Biology·Tracy DoanRaymond J Steptoe
Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jason PereraHaochu Huang

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