New polymorphic microsatellite markers in the human MHC class II region

Matsuzaka, Yasunari; Makino, Satoshi; Nakajima, K.; Tomizawa, M.; Oka, Akira; Kimura, Minoru; Bahram, Seiamak; Tamiya, Gen; Inoko, H

doi:10.1034/j.1399-0039.2000.560602.x

Cited by 26 publications

(31 citation statements)

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“…The RPD [55][56][57] epitope is associated with protection; however, the individual residues R, P, and D, when evaluated independently, are not. This is reminiscent of the association of rheumatoid arthritis with the residues DR␤ 67 , DR␤ 70 , DR␤ 71 , and DR␤ 74 together, but not any of these residues independently (42).…”

Section: Discussionmentioning

confidence: 99%

“…Regardless of the role of this DR epitope, whether it is part of a binding pocket of an HLA molecule or part of a peptide bound to an HLA molecule, this epitope operates as a defined sequence and not as individual residues. The RPD [55][56][57] epitope of this study is also located in a position that is known to influence peptide binding and T cell recognition. Residue 57 participates in the formation of a pocket 9 of DQ molecules and is associated with susceptibility to insulindependent diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

“…The specific epitopes identified as disease protection is the DQ␤ RPD [55][56][57] and susceptibility are the DQ␤ L 56 /ED 70 -71 /DR␤E 9 V 11 H 13 epitopes, respectively. There are a number of interesting points with respect to these epitopes and their role in AIDP.…”

Section: Discussionmentioning

confidence: 99%

“…Since position 57 of the DQ␤-chain has been implicated in disease susceptibility, for example, in insulin-dependent diabetes mellitus (46), it is possible that this DQ␤ position may be critical to other diseases as well. Analysis of the RPD [55][56][57] epitope was therefore performed and showed that this epitope was significantly reduced among AIDP cases compared with either control ( p ϭ 0.05) or AMAN ( p ϭ 0.036) cases (Table IV). When R 55 , P 56 , and D 57 were analyzed as individual amino acids there were no significant differences among the populations studied.…”

Section: Differential Distribution Of Dqb1 Amino Acid Epitopes Among mentioning

confidence: 99%

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Differential Distribution of HLA-DQβ/DRβ Epitopes in the Two Forms of Guillain-Barré Syndrome, Acute Motor Axonal Neuropathy and Acute Inflammatory Demyelinating Polyneuropathy (AIDP): Identification of DQβ Epitopes Associated with Susceptibility to and Protection from AIDP

Magira

Papaioakim²,

Nachamkin³

et al. 2003

The Journal of Immunology

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Guillain-Barré syndrome (GBS), an acute, immune-mediated paralytic disorder affecting the peripheral nervous system, is the most common cause of acute flaccid paralysis in the postpolio era. GBS is classified into several subtypes based on clinical and pathologic criteria, with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) being the most common forms observed. To better understand the pathogenesis of GBS and host susceptibility to developing the disease, the distribution of HLA class II Ags along with the seroreactivity to Campylobacter jejuni were investigated in a population of GBS patients from northern China. Using DNA-based typing methods, 47 patients with AMAN, 25 patients with AIDP, and 97 healthy controls were studied for the distribution of class II alleles. We found that the DQβ RLD55–57/ED70–71 and DRβ E9V11H13 epitopes were associated with susceptibility to AIDP (p = 0.009 and p = 0.004, respectively), and the DQβ RPD55–57 epitope was associated with protection (p = 0.05) from AIDP. These DQβ/DRβ positional residues are a part of pockets 4 (DQβ 70, 71, DRβ13), 6 (DRβ11), and 9 (DQβ 56, 57, DRβ9); have been demonstrated to be important in peptide binding and T cell recognition; and are associated with other diseases that have a pathoimmunological basis. Class II HLA associations were not identified with AMAN, suggesting a different immunological mechanism of disease induction in the two forms of GBS. These findings provide immunogenetic evidence for differentiating the two disease entities (AMAN and AIDP) and focuses our attention on particular DRβ/DQβ residues that may be instrumental in understanding the pathophysiology of AIDP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Differential Distribution Of Dqb1 Amino Acid Epitopes Among mentioning

confidence: 99%

See 2 more Smart Citations

Differential Distribution of HLA-DQβ/DRβ Epitopes in the Two Forms of Guillain-Barré Syndrome, Acute Motor Axonal Neuropathy and Acute Inflammatory Demyelinating Polyneuropathy (AIDP): Identification of DQβ Epitopes Associated with Susceptibility to and Protection from AIDP

Magira

Papaioakim²,

Nachamkin³

et al. 2003

The Journal of Immunology

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“…More than 1000 polymorphic microsatellite markers have been described within the HLA region. [13][14][15][16] The microsatellite markers showed considerable polymorphism and strong LD with particular alleles of classical HLA loci composing of well-defined extended HLA haplotypes. 17 The HLA haplotypes can be separated into several blocks, including a haplotype block containing the HLA-Cw and -B genes, just centromeric to the MHC class I region, which is known to be one of the highest polymorphic loci in the human genome.…”

Section: Introductionmentioning

confidence: 99%

Complex divergence at a microsatellite marker C1_2_5 in the lineage of HLA-Cw/-B haplotype

et al. 2009

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The human leukocyte antigen (HLA) complex locus has shaped a framework for evolutionary processes because of the dense clustering and strong linkage disequilibrium (LD) of polymorphic genes. Although the landscape of LD among conventional single-nucleotide polymorphisms (SNPs) has been described, the data on the lineage of major histocompatibility complex (MHC) haplotype are limited to pairwise comparisons of several haplotypes in Caucasoid populations. Multi-allelic markers, including microsatellite markers, may provide us with a larger power to analyze the MHC haplotype lineage because the mutation rate of microsatellite exceeds that of SNPs by several orders of magnitude. In this study, we investigated the complex structure of repeat motifs in a microsatellite to figure out the structural lineage of HLA-Cw/-B segments in Japanese. It was found that the genetic differences of HLA-Cw/-B haplotype lineage were reflected by repeat motif patterns at C1_2_5 locus, suggesting that unique mutational dynamics of microsatellites may be a useful marker to chase the haplotype lineage.

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A second major histocompatibility complex susceptibility locus for multiple sclerosis

Yeo¹,

Jager²,

Gregory³

et al. 2007

Annals of Neurology

157

113

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ObjectiveVariation in the major histocompatibility complex (MHC) on chromosome 6p21 is known to influence susceptibility to multiple sclerosis with the strongest effect originating from the HLA-DRB1 gene in the class II region. The possibility that other genes in the MHC independently influence susceptibility to multiple sclerosis has been suggested but remains unconfirmed.MethodsUsing a combination of microsatellite, single nucleotide polymorphism, and human leukocyte antigen (HLA) typing, we screened the MHC in trio families looking for evidence of residual association above and beyond that attributable to the established DRB1*1501 risk haplotype. We then refined this analysis by extending the genotyping of classical HLA loci into independent cases and control subjects.ResultsScreening confirmed the presence of residual association and suggested that this was maximal in the region of the HLA-C gene. Extending analysis of the classical loci confirmed that this residual association is partly due to allelic heterogeneity at the HLA-DRB1 locus, but also reflects an independent effect from the HLA-C gene. Specifically, the HLA-C*05 allele, or a variant in tight linkage disequilibrium with it, appears to exert a protective effect (p = 3.3 × 10−5).InterpretationVariation in the HLA-C gene influences susceptibility to multiple sclerosis independently of any effect attributable to the nearby HLA-DRB1 gene. Ann Neurol 2007

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New polymorphic microsatellite markers in the human MHC class II region

Cited by 26 publications

References 0 publications

Differential Distribution of HLA-DQβ/DRβ Epitopes in the Two Forms of Guillain-Barré Syndrome, Acute Motor Axonal Neuropathy and Acute Inflammatory Demyelinating Polyneuropathy (AIDP): Identification of DQβ Epitopes Associated with Susceptibility to and Protection from AIDP

Differential Distribution of HLA-DQβ/DRβ Epitopes in the Two Forms of Guillain-Barré Syndrome, Acute Motor Axonal Neuropathy and Acute Inflammatory Demyelinating Polyneuropathy (AIDP): Identification of DQβ Epitopes Associated with Susceptibility to and Protection from AIDP

Complex divergence at a microsatellite marker C1_2_5 in the lineage of HLA-Cw/-B haplotype

A second major histocompatibility complex susceptibility locus for multiple sclerosis

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