Haplotypic variation of the transporter associated with antigen processing (TAP) genes and their extension of HLA class II region haplotypes

Abstract

Stable cell surface presentation of HLA class I molecules requires active transport of antigenic peptides across the endoplasmic reticulum by products of two genes, TAP1 and TAP2, which map in the major histocompatibility complex class II region. Alleles of each gene are derived from a combination of variable sites at each locus. In this study, TAP1 and TAP2 alleles were identified in homozygous typing cell (HTC) lines, allowing resolution of specific haplotypes in conjunction with the highly polymorphic HLA class II region haplotypes. Three alleles at each TAP locus were found from which eight haplotypes could be assigned. Determination of TAP1 and TAP2 alleles in cell lines homozygous at DR, DQ, and DP created eight additional haplotypes beyond the number observed with these class II genes alone. Complete analysis of DR, DQ, TAP, and DP genotypes in 66 HTCs resulted in the following groups: 1) 46 homozygotes; 2) nine homozygous at DR, DQ, and TAP, but heterozygous at DP; 3) four homozygous at DR, DQ, and DP, but heterozygous at one or both TAP genes; 4) four homozygous at DR and DQ, but heterozygous at TAP and DP; and 5) three complex genotypes heterozygous at DP, TAP, and at least one of DQA1, DQB1, or DRB1 loci. TAP1 and TAP2 genes map in an area of frequent recombination. TAP alleles were determined in five DQB1, DPB1 recombinant individuals, three of which were informative. Recombination was found between DQB1 and the TAP loci in two individuals and between TAP and DPB1 in the other individual.

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

“…Previous studies have shown that there is no strong LD between the TAP1 and TAP2 genes or between TAP1/TAP2 and HLA class II genes in Caucasians. 49,50 This may reflect the recombinational hot spot located in TAP2. 51 Nevertheless, certain HLA-DR-DQ haplotypes extend to include the TAP alleles 49 and there is a possibility that TAP associations with disease could reflect HLA effects; there are several reports where putative associations are dependent on HLA alleles and likely to be caused by LD with HLA genes.…”

“…49,50 This may reflect the recombinational hot spot located in TAP2. 51 Nevertheless, certain HLA-DR-DQ haplotypes extend to include the TAP alleles 49 and there is a possibility that TAP associations with disease could reflect HLA effects; there are several reports where putative associations are dependent on HLA alleles and likely to be caused by LD with HLA genes. 27,52,53 To determine if the association of the TAP2 665 SNP with cervical cancer depended on DQB1, we stratified the cases and controls based on positivity for DQB1 alleles.…”

Epstein-Barr Virus Isolates Retain Their Capacity To Evade T Cell Immunity through BNLF2a despite Extensive Sequence Variation

“…One might expect the less-efficient BNLF2a variants to succumb during viral evolution. However, considering the polymorphism that is observed for TAP (6,8,22,23,29), it is not surprising to find variants of the TAP inhibitor BNLF2a as well. Whether these BNLF2a mutants have different efficiencies for inhibiting the various TAP alleles remains to be determined.…”

HLA-DR, HLA-DQ, and TAP genes in familial Hodgkin disease

“…The single-strand conformational polymorphism assays used to determine subjects' genotypes have been described for DQA1, 17 DQB1, 17 DRB1, 18 DRD3, 18 DRB4, 18 DRB5, 18 TAP1, 19 and TAP2. 19 The individual DRB1 For personal use only. on May 9, 2018. by guest www.bloodjournal.org From alleles within the DR13 and DR14 groups (serogroups or lineages) were not subtyped at the allele level.…”