Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex

Viken, Marte K.; Blomhoff, Anne; Olsson, Marita; Akselsen, Hanne E.; Pociot, Flemming; Nerup, Jørn; Kockum, Ingrid; Cambon‐Thomsen, Anne; Thorsby, E.; Undlien, D E; Lie, Benedicte A.

doi:10.1038/gene.2009.13

Cited by 41 publications

(29 citation statements)

References 50 publications

(75 reference statements)

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“…The sequences show approximately 90% amino acid identity within each family and approximately 50% between families (26). The extended MHC region encompassing the human BTN gene cluster has been linked to type 1 diabetes by genetic analysis (27). The conserved MOG (myelin oligodendrocyte glycoprotein) gene, positioned nearer to MHC class I genes, shares sequence homology with BTN and is also considered to be part of the butyrophilin gene family.…”

Section: S K I N T 8 S K I N T 7 S K I N T 1 Skint4 Skint3 Skint9 Skint2mentioning

confidence: 99%

Regulation of Immunity by Butyrophilins

Rhodes

Reith

Trowsdale

2016

Annu. Rev. Immunol.

129

137

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Butyrophilin molecules (commonly contracted to BTN), collectively take their name from the eponymous protein in cow's milk. They are considered to be members of the B7 family of costimulatory receptors, which includes B7.1 (CD80), B7.2 (CD86), and related molecules, such as PD-L1 (B7-H1, CD274), ICOS-L (CD275), and B7-H3 (CD276). These coreceptors modulate T cell responses upon antigen presentation by major histocompatibility complex and cognate αβ T cell receptor engagement. Molecules such as BTN3A1 (CD277), myelin oligodendrocyte glycoprotein, and mouse Skint1 and Btnl2, all members of the butyrophilin family, show greater structural and functional diversity than the canonical B7 receptors. Some butyrophilins mediate complex interactions between antigen-presenting cells and conventional αβ T cells, and others regulate the immune responses of specific γδ T cell subsets by mechanisms that have characteristics of both innate and adaptive immunity.

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Section: S K I N T 8 S K I N T 7 S K I N T 1 Skint4 Skint3 Skint9 Skint2mentioning

confidence: 99%

Regulation of Immunity by Butyrophilins

Rhodes

Reith

Trowsdale

2016

Annu. Rev. Immunol.

129

137

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“…PRSS16 was initially described as a gene of the extended HLA region linked to a diabetes susceptibility locus in humans (6,7). PRSS16 encodes a serine protease, thymus-specific serine protease (TSSP), that belongs to the family of lysosomal ProXaa serine exopeptidases that includes lysosomal prolyl carboxypeptidase and dipeptidyl peptidase II/VII.…”

Section: Introductionmentioning

confidence: 99%

Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice

Viret¹,

Leung–Theung–Long²,

Serre³

et al. 2011

J. Clin. Invest.

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Type 1 diabetes is a chronic autoimmune disease in which genetic predispositions affect the immune system, leading to a loss of T cell tolerance to β cells and consequent T cell-mediated destruction of insulin-producing islet cells. Genetic studies have suggested that PRSS16 is linked to a diabetes susceptibility locus of the extended HLA class I region in humans. PRSS16 encodes what we believe to be a novel protease, thymus-specific serine protease (TSSP), which shows predominant expression in thymic epithelial cells and is suspected to have a restricted role in the class II presentation pathway. Consistently, Tssp is necessary for the intrathymic selection of few class II-restricted T cell receptor specificities in B6 mice. To directly assess the role of Tssp in autoimmune diabetes, we generated Tssp-deficient (Tssp°) NOD mice. While remaining immunocompetent, Tssp° NOD mice were protected from diabetes and severe insulitis. Diabetes resistance of Tssp° NOD mice was a property of the CD4 T cell compartment that is acquired during thymic selection and correlated with an impaired selection of CD4 T cells specific for islet antigens. Hence, in the NOD mouse, Tssp is a critical regulator of diabetes development through the selection of the autoreactive CD4 T cell repertoire.

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“…Interestingly, the BTN gene cluster has been also associated with type 1 diabetes. 38 The BTN cluster encodes proteins of as yet unknown functions, but they are thought to have an immunological role, given that they show strong similarity with other xMHC genes and with CD80 and CD86 costimulatory receptors. 39,40 Regarding the association found in the HLA-B-HCP5 locus for anti-CCP þ patients, it is difficult to ascertain whether it represents a different effect from that found in Corf26-RDBP in the non-stratified analysis (Figures 2a and b).…”

Section: Discussionmentioning

confidence: 99%