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Distinct spatial relationship of the interleukin-9 receptor with interleukin-2 receptor and major histocompatibility complex glycoproteins in human T lymphoma cells.

ABSTRACT: The interleukin-9 receptor (IL-9R) consists of an ? subunit and a ?(c) chain that are shared with other cytokine receptors, including interleukin-2 receptor (IL-2R), an important regulator of T cells. We previously showed that IL-2R is expressed in common clusters with major histocompatibility complex (MHC) glycoproteins in lipid rafts of human T lymphoma cells, which raised the question about what the relationship between clusters of IL-2R/MHC and IL-9R is. Confocal microscopy colocalization and fluorescence resonance energy transfer experiments capable of detecting membrane protein organization at different size scales revealed nonrandom association of IL-9R with IL-2R/MHC clusters at the surface of human T lymphoma cells. Accommodation of IL-9R? in membrane areas segregated from the IL-2R/MHC domains was also detected. The bipartite nature of IL-9R distribution was mirrored by signal transducer and activator of transcription (STAT) activation results. Our data indicate that co-compartmentalization with MHC glycoproteins is a general property of ?(c) receptors. Distribution of receptor chains between different membrane domains may regulate their function.

SUBMITTER: Nizsaloczki E

PROVIDER: S-EPMC4457943 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Distinct spatial relationship of the interleukin-9 receptor with interleukin-2 receptor and major histocompatibility complex glycoproteins in human T lymphoma cells.

Nizsalóczki Enikő E Csomós István I Nagy Péter P Fazekas Zsolt Z Goldman Carolyn K CK Waldmann Thomas A TA Damjanovich Sándor S Vámosi György G Mátyus László L Bodnár Andrea A

Chemphyschem : a European journal of chemical physics and physical chemistry 20141008 18

The interleukin-9 receptor (IL-9R) consists of an α subunit and a γ(c) chain that are shared with other cytokine receptors, including interleukin-2 receptor (IL-2R), an important regulator of T cells. We previously showed that IL-2R is expressed in common clusters with major histocompatibility complex (MHC) glycoproteins in lipid rafts of human T lymphoma cells, which raised the question about what the relationship between clusters of IL-2R/MHC and IL-9R is. Confocal microscopy colocalization an ...[more]

PMID: 25297818

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Project description:To determine the relationship between highly-conserved extended-haplotypes (CEHs) in the major histocompatibility complex (MHC) and MS-susceptibility.Among the ~200 MS-susceptibility regions, which are known from genome-wide analyses of single nucleotide polymorphisms (SNPs), the MHC accounts for roughly a third of the currently explained variance and the strongest MS-associations are for certain Class II alleles (e.g., HLA-DRB1*15:01; HLA-DRB1*03:01; and HLA-DRB1*13:03), which frequently reside on CEHs within the MHC.Autosomal SNPs (441,547) from 11,376 MS cases and 18,872 controls in the WTCCC dataset were phased. The most significant MS associated SNP haplotype was composed of 11 SNPs in the MHC Class II region surrounding the HLA-DRB1 gene. We also phased alleles at the HLA-A, HLA-C, HLA-B, HLA-DRB1, and HLA-DQB1 loci. This data was used to probe the relationship between CEHs and MS susceptibility.We phased a total of 59,884 extended haplotypes (HLA-A, HLA-C, HLA-B, HLA-DRB1, HLA-DQB1 and SNP haplotypes) from 29,942 individuals. Of these, 10,078 unique extended haplotypes were identified. The 10 most common CEHs accounted for 22% (13,302) of the total. By contrast, the 8,446 least common extended haplotypes also accounted for approximately 20% (12,298) of the total. This extreme frequency-disparity among extended haplotypes necessarily complicates interpretation of reported disease-associations with specific HLA alleles. In particular, the HLA motif HLA-DRB1*15:01~HLA-DQB1*06:02 is strongly associated with MS risk. Nevertheless, although this motif is almost always found on the a1 SNP haplotype, it can rarely be found on others (e.g., a27 and a36), and, in these cases, it seems to have no apparent disease-association (OR = 0.7; CI = 0.3-1.3 and OR = 0.7; CI = 0.2-2.2, respectively). Furthermore, single copy carriers of the a1 SNP-haplotype without this HLA motif still have an increased disease risk (OR = 2.2; CI = 1.2-3.8). In addition, even among the set of CEHs, which carry the Class II motif of HLA-DRB1*15:01~HLA-DQB1*06:02~a1, different CEHs have differing strengths in their MS-associations.The MHC in diverse human populations consists, primarily, of a very small collection of very highly-selected CEHs. Our findings suggest that the MS-association with the HLA-DRB1*15:01~HLA-DQB1*06:02 haplotype may be due primarily to the combined attributes of the CEHs on which this particular HLA-motif often resides.

Dataset Information

Distinct spatial relationship of the interleukin-9 receptor with interleukin-2 receptor and major histocompatibility complex glycoproteins in human T lymphoma cells.

Publications

Distinct spatial relationship of the interleukin-9 receptor with interleukin-2 receptor and major histocompatibility complex glycoproteins in human T lymphoma cells.

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