Regulation of costimulation in the era of butyrophilins

Arnett, Heather A.; Escobar, Sabine; Viney, Joanne L.

doi:10.1016/j.cyto.2009.03.009

Cited by 61 publications

(65 citation statements)

References 49 publications

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“…BTN2A1 is a cell surface transmembrane glycoprotein that is a member of the butyrophilin superfamily. The butyrophilin family was originally identified due to its ability to induce the production of milk fat globules (15), however, a number of proteins belonging to the butyrophilin and butyrophilin-like families were shown to regulate immune function and polymorphisms in the protein coding sequences were associated with the predisposition to inflammatory diseases (16). Our previous study showed that the T allele of the rs6929846 polymorphism of the BTN2A1 gene was associated with an increased risk of myocardial infarction and with an increased transcription activity of BTN2A1 (9).…”

Section: Discussionmentioning

confidence: 99%

Association of a butyrophilin, subfamily 2, member A1 gene polymorphism with hypertension

2014

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Abstract. The C→T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 (BTN2A1) gene has been previously identified as a susceptibility locus for myocardial infarction by a genome-wide association study. As hypertension is a major risk factor for myocardial infarction, the association between the BTN2A1 polymorphism, rs6929846, and myocardial infarction may be partly due to its effect on hypertension susceptibility. The aim of the present study was to examine the possible association of rs6929846 with hypertension. The study subjects comprised 5,959 community-dwelling individuals (2,183 subjects with hypertension and 3,776 controls) who were recruited to a population-based cohort study. The rs6929846 genotype was determined by a method that combined polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons between the genotype distributions (P= 0.0090) and allele frequencies (P= 0.0051) by the χ 2 test revealed that rs6929846 was significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that rs6929846 was significantly associated with hypertension (P=0.0008; odds ratio, 1.29; dominant model), with the minor T allele representing a risk factor for this condition. Among all the individuals, systolic, diastolic and mean blood pressure was significantly higher in the combined group of individuals with the CT or TT genotypes compared to the CC genotype group. BTN2A1 may thus be a susceptibility gene for hypertension. Therefore, determining the genotype for this polymorphism may provide genetic risk assessment information for hypertension.

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Section: Discussionmentioning

confidence: 99%

Association of a butyrophilin, subfamily 2, member A1 gene polymorphism with hypertension

2014

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“…BTNs are type I membrane glycoproteins that were initially identified in bovine milk fat globules (11). BTNs are located at the extended major histocompatibility complex region in chromosome 6, constitute the immunoglobulin superfamily together with the B7 gene family and butyrophilin-like gene (BTNL) family, and are widely expressed in a variety of human immune cells, suggesting a possible role in immune functions (12). Previous studies have shown significant relations of polymorphisms of BTNL2 with Kawasaki disease in Taiwanese children (13) and sarcoidosis in German (14) and American (15) populations, both of which are caused by inflammatory autoimmune responses.…”

Section: Discussionmentioning

confidence: 99%

Association of a polymorphism of BTN2A1 with dyslipidemia in East Asian populations

Fujimaki

Kato

Oguri³

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. We previously identified rs6929846 of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) as a susceptibility locus for myocardial infarction in Japanese individuals by a genome-wide association study. The aim of the present study was to examine the relation of the rs6929846 polymorphism of BTN2A1 to dyslipidemia in Japanese and Korean populations, given that dyslipidemia is an important risk factor for myocardial infarction. A total of 10,953 individuals from three independent subject panels were examined. The relations of the rs6929846 polymorphism of BTN2A1 to serum concentrations of triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol were examined in each subject panel. The C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with serum concentrations of triglycerides in Japanese subject panels A (P=0.0004) and B (P=0.0010), and in the Korean population (P=0.0095), with the minor T allele being related to an increased serum concentration of triglycerides. The rs6929846 was associated with serum concentrations of HDL-cholesterol in Japanese subject panels A (P=0.0047) and B (P=0.0015), with the T allele being related to a decreased serum concentration of HDL-cholesterol, but not in the Korean population. This polymorphism was associated with the serum concentration of LDL-cholesterol only in Japanese subject panel B (P=0.0059), with the T allele being related to an increased serum concentration of LDL-cholesterol. The results suggest that BTN2A1 may be a susceptibility gene for hypertriglyceridemia in East Asian populations and for low serum HDL-cholesterol in the Japanese population.

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“…These proteins have important functions in immune regulation, acting as co-stimulatory molecules (B7-1 and B7-2) for T cell activation and potent inhibitory molecules (PD-L1) to down-regulate T cell responses (14). The B7-related butyrophilin and butyrophilin-like proteins have recently been more fully characterized, revealing a range of immune and nonimmune related functions (15)(16)(17)(18)(19). Application of an antibody specific to a subclass of BTN proteins, CD277/butyrophilin-3 (BTN3A) (15), induced strong stimulation of V␥9V␦2 T cells (13).…”

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confidence: 99%

The Molecular Basis for Modulation of Human Vγ9Vδ2 T Cell Responses by CD277/Butyrophilin-3 (BTN3A)-specific Antibodies

Palakodeti

Sandstrom

Sundaresan

et al. 2012

Journal of Biological Chemistry

153

203

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Background: Phosphoisoprenoid stimulation of V␥9V␦2 T cells can be modulated by anti-BTNA3 antibodies. Results: Agonist and antagonist antibodies associate differently with BTN3A structurally and biophysically. Conclusion: Differential binding of antibodies to BTN3A modulates its oligomerization on the cell surface. Significance: Defining how ␥␦ T cells recognize antigen is critical for understanding their functions in the immune response.

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Regulation of costimulation in the era of butyrophilins

Cited by 61 publications

References 49 publications

Association of a butyrophilin, subfamily 2, member A1 gene polymorphism with hypertension

Association of a butyrophilin, subfamily 2, member A1 gene polymorphism with hypertension

Association of a polymorphism of BTN2A1 with dyslipidemia in East Asian populations

The Molecular Basis for Modulation of Human Vγ9Vδ2 T Cell Responses by CD277/Butyrophilin-3 (BTN3A)-specific Antibodies

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