Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule

Powis, Simon J.; Ev, Deverson; Wj, Coadwell; Ciruela, Antonio; Ns, Huskisson; Smith, Helen; Gw, Butcher; Jc, Howard

doi:10.1038/357211a0

Cited by 329 publications

(146 citation statements)

References 42 publications

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“…Distinctive allelic lineages of TAP2 and linkage disequilibrium between class Ia and TAP2 genes were previously reported in rats [8,9] and chickens [10]. Peptides transported by the 'restrictive' rat TAP2B presumably can be loaded onto TAP2B-linked class I molecules more efficiently [11][12][13].…”

Section: Introductionmentioning

confidence: 84%

Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co‐evolution among MHC class I region genes

et al. 2003

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In the frog Xenopus, MHC class I antigen presentation and processing genes (the immunoproteasome LMP2 and LMP7 and the transporter TAP1 and TAP2) seem to be closely linked in a primordial organization. Two distinct lineages of class Ia and LMP7 loci were previously identified, thus strongly suggesting co-evolution among 'class I region' genes. We now show that the Xenopus MHC 'class I region' lies between class II and class III genes and we have isolated two distinct alleles at both the TAP1 and TAP2 loci. The alleles at each locus are remarkably divergent from each other and phylogenetic tree analysis revealed in both cases that they diverged from each other 60-100 million years ago (MYA). For lineage-frequency and linkage analysis, 25 wild-caught X. laevis and 16 X. tropicalis were examined. The two lineages were present in different frequencies for X. laevis and X. tropicalis. Nevertheless, in all cases, the LMP7, TAP1, and TAP2 lineages were found in a set comprising one of the two lineages. Furthermore, like the LMP7 lineages, the TAP lineages were detected in most Xenopus species that diverged from a common ancestor 80-100 MYA, suggesting that the 'class I region' biallelic lineages are under balancing selection.

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Section: Introductionmentioning

confidence: 84%

Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co‐evolution among MHC class I region genes

et al. 2003

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“…In rat, it has been shown that TAP2 polymorphisms could affect peptide transfer. 47 Human TAP genes are less polymorphic and this polymorphism does not seem to alter peptide transport. 48 The interallelic LD between TAP2 665 and the DQB1 alleles associated with cervical cancer made it difficult to exclude the possibility that the TAP2 665 association with cervical cancer was due to LD with specific alleles at HLA-DQB1.…”

Section: Discussionmentioning

confidence: 99%

MHC loci affecting cervical cancer risk: distinguishing the effects of HLA-DQB1 and non-HLA genes TNF, LTA, TAP1 and TAP2

Ivansson

Magnusson

et al. 2008

Genes Immun

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Cervical cancer has been associated with specific human leukocyte antigen (HLA) haplotypes/alleles and with polymorphisms at the nearby non-HLA loci TNF, LTA, TAP1 and TAP2. Distinguishing effects of individual loci in the major histocompatibility complex (MHC) region are difficult due to the complex linkage disequilibrium (LD) pattern characterized by high LD, punctuated by recombination hot spots. We have evaluated the association of polymorphism at HLA class II DQB1 and the TNF, LTA, TAP1 and TAP2 genes with cervical cancer risk, using 1306 familial cases and 288 controls. DQB1 was strongly associated; alleles *0301, *0402 and *0602 increased cancer susceptibility, whereas *0501 and *0603 decreased susceptibility. Among the non-HLA loci, association was only detected for the TAP2 665 polymorphism, and interallelic disequilibrium analysis indicated that this could be due to LD with DQB1. As the TAP2 665 association was seen predominantly in non-carriers of DQB1 susceptibility alleles, we hypothesized that TAP2 665 may have an effect not attributable to LD with DQB1. However, a logistic regression analysis suggested that TAP2 665 was strongly influenced by LD with DQB1. Our results emphasize the importance of large sample sizes and underscore the necessity of examining both HLA and non-HLA loci in the MHC to assign association to the correct locus.

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“…15 Evidence for the first phenomenon comes from studies showing many variations in rat TAP genes that have been associated with differences in the spectrum of MHC class I peptides transported and presented to the T cell receptor (TCR). 16 In contrast, human TAP genes carry relatively limited polymorphism and when different TAP allelic combinations were analysed, 17,18 no difference in the spectrum of transported peptides was shown. However, it has been suggested that alleles carrying Asp/637 (charged polar residue) appeared to be more restrictive in transporting peptides than those carrying Gly/637 (nonpolar residue).…”

Section: Introductionmentioning

confidence: 99%

Distribution of TAP gene polymorphisms and extended MHC haplotypes in Mexican Mestizos and in Seri Indians from northwest Mexico

et al. 2002

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Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule

Cited by 329 publications

References 42 publications

Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co‐evolution among MHC class I region genes

Two highly divergent ancient allelic lineages of the transporter associated with antigen processing (TAP) gene in Xenopus: further evidence for co‐evolution among MHC class I region genes

MHC loci affecting cervical cancer risk: distinguishing the effects of HLA-DQB1 and non-HLA genes TNF, LTA, TAP1 and TAP2

Distribution of TAP gene polymorphisms and extended MHC haplotypes in Mexican Mestizos and in Seri Indians from northwest Mexico

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