A novel HLA-B27 allele maps B27 allospecificity to the region around position 70 in the alpha 1 domain.
A novel HLA-B27 allele maps B27 allospecificity to the region around position 70 in the alpha 1 domain.
复制标题
一种新的 HLA-B27 等位基因将 B27 同种异体特异性映射到 alpha 1 结构域中位置 70 周围的区域。
作者：
S. Choo;L. Fan;J. Hansen
有六个已知的HLA-B等位基因具有HLA-B27同种特异性，但存在一到六个氨基酸取代的差异。这些B27等位基因中的每一个都可以很容易地通过六种代表性IEF模式之一来分配。两个不相关的个体，LH和HS，表达B27 Ag，通过IEF似乎是相同的，但是发现HLA-B27同种异体反应性CTL克隆I-73与这些细胞反应不同，表明这些B27分子是不相同的。我们对从HS中获得的B27 cDNA克隆进行了聚合酶链反应扩增，并将其推导的氨基酸序列（B27-HS）与LH的B27序列（B27-LH）进行了比较，后者先前被指定为B*2701等位基因。B27-HS和B27-LH相差8个氨基酸; 3个在α 1结构域，5个在α 2结构域。B27-HS的这些氨基酸取代改变了T细胞识别，但不改变B27血清学表位或IEF模式。B27-HS与六个已知的B27等位基因的不同之处在于五至八个氨基酸取代，因此它代表HLA-B27 Ag家族的第七个等位基因。这种新的B27等位基因可能来自基因转换事件。以前，在位置70和97处的两个氨基酸残基被认为是B27 Ag家族的特异性。B27-HS现在揭示了位置70处的Lys对B27是特异性的，但位置97处的Asn不是。我们建议，位置70周围的区域可能是至关重要的，在确定B27血清表位，并可能在肽Ag结合。这项研究还表明，具有相同Ag特异性的I类分子共享不可区分的IEF模式不一定是相同的，并表明只有确定的一级结构将确定所有I类等位基因的功能相关的同种异体反应性，T细胞限制性，和疾病的关联。
There are six known HLA-B alleles that share the HLA-B27 allospecificity, yet differ by one to six amino acid substitutions. Each of these B27 alleles can be readily assigned by one of the six representative IEF patterns. Two unrelated individuals, LH and HS, express B27 Ag that appear to be identical by IEF, but an HLA-B27 alloreactive CTL clone I-73 was found to react differently with these cells, suggesting these B27 molecules are not identical. We sequenced polymerase chain reaction-amplified B27 cDNA clones obtained from HS and compared its deduced amino acid sequence (B27-HS) with the B27 sequence of LH (B27-LH) which was previously designated the B*2701 allele. B27-HS and B27-LH differ by eight amino acids; three in alpha 1 domain and five in alpha 2 domain. These amino acid substitutions of B27-HS altered T cell recognition but not the B27 serologic epitope or IEF pattern. B27-HS differs from the six known B27 alleles by five to eight amino acid substitutions, and thus it represents the seventh allele of the HLA-B27 Ag family. This novel B27 allele might have been derived from a gene conversion event. Previously, two amino acid residues at positions 70 and 97 were suggested to be specific for B27 Ag family. B27-HS now reveals that Lys at position 70 is specific for B27 but Asn at position 97 is not. We propose that the region around position 70 might be crucial in determining the B27 serologic epitope and possibly in peptide Ag binding. This study also demonstrates that class I molecules of the same Ag specificity sharing an indistinguishable IEF pattern are not necessarily identical, and indicates that only the definitive determination of primary structure would identify all the class I alleles that are functionally relevant in regard to alloreactivity, T cell restriction, and disease association.