Carrington M, Colonna M, Spies T, Stephens J C, Mann D L
Program Resources, Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201.
Immunogenetics. 1993;37(4):266-73. doi: 10.1007/BF00187452.
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.
HLA I类分子在细胞表面的稳定呈递需要抗原肽通过TAP1和TAP2这两个基因的产物在内质网中进行主动转运，这两个基因定位于主要组织相容性复合体II类区域。每个基因的等位基因来自每个位点可变位点的组合。在本研究中，在纯合分型细胞（HTC）系中鉴定了TAP1和TAP2等位基因，结合高度多态的HLA II类区域单倍型，可解析特定单倍型。在每个TAP位点发现了三个等位基因，由此可确定八种单倍型。在DR、DQ和DP位点纯合的细胞系中确定TAP1和TAP2等位基因，除了仅这些II类基因观察到的单倍型数量外，又产生了八种额外的单倍型。对66个HTC细胞系的DR、DQ、TAP和DP基因型进行完整分析，得到以下几组：1）46个纯合子；2）9个在DR、DQ和TAP位点纯合，但在DP位点杂合；3）4个在DR、DQ和DP位点纯合，但在一个或两个TAP基因位点杂合；4）4个在DR和DQ位点纯合，但在TAP和DP位点杂合；5）3个复杂基因型，在DP、TAP以及DQA1、DQB1或DRB1位点中的至少一个位点杂合。TAP1和TAP2基因定位于频繁发生重组的区域。在五个DQB1、DPB1重组个体中确定了TAP等位基因，其中三个个体提供了信息。在两个个体中发现DQB1和TAP位点之间发生了重组，在另一个个体中发现TAP和DPB1位点之间发生了重组。
