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Granuloma resolution or progression in sarcoidosis: Exposure to an unknown antigen or antigens leads to either resolution or progression. Granuloma resolution (immune response 1) occurs when peptide antigens are presented by human leukocyte antigen (HLA)-DR3 molecules on dendritic cells or macrophages and recognized by a specific T cell receptor (TCR) β-chain variable segment 8 (TRBV8) and α-chain variable 2.3 (TRAV2.3) and CD4-positive (TRAV2.3+TRBV22+CD4+) T cells. An efficient immune response is generated that involves the production of a large range of cytokines, and the antigen is eliminated and the granuloma resolves. Conversely, granuloma progression (immune response 2) occurs if antigen recognition is not efficient, possibly because other peptides are displayed by HLA molecules other than HLADRB1*03 (HLA-DR3) or T cells are not capable of generating efficient T cell clones. Consequently, granulomas continue to grow and the disease persists. | APC, antigen-presenting cell; MHC, major histocompatibility complex. | Grunewald, J., Grutters, J. C., Arkema, E. V, Saketkoo, L. A., Moller, D. R., & Müller-Quernheim, J. (2019). Sarcoidosis. Nature Reviews Disease Primers, 5(1), 45. https://doi.org/10.1038/s41572-019-0096-x

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