Castaño R, Ezquerra A, Doménech N, López de Castro J A
Department of Immunology, Fundación Jiménez Díaz, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Immunogenetics. 1988;27(5):345-55. doi: 10.1007/BF00395130.
The HLA-A2 antigen expressed by donor OZB can be distinguished from the main HLA-A2.1 subtype by isoelectric focusing - it is one charge unit more acidic - and by some alloreactive T-cell clones but not by cytolytic T lymphocyte lines. The structure of variant OZB has been examined by comparative peptide mapping with A2.1 and radiochemical sequence analysis. The two molecules were found to differ in a single tryptic peptide from the alpha 3 region, spanning residues 220-243. The amino acid sequence of this peptide from variant OZB revealed that there was only one amino acid change of Glu instead of Ala at position 236, a hitherto invariant residue in class I HLA antigens. All previously characterized HLA or H-2 natural variants have structural changes restricted to the alpha 1 and/or alpha 2 domains. Thus, variant OZB is unique in that (1) it has one amino acid change in alpha 3 and (2) it has no changes in alpha 1 and alpha 2. The only detected substitution of this variant may be accounted for by a single base change at the DNA level, suggesting that it might have resulted from a point mutation in the A2.1 gene. The structural features of variant OZB open a novel way to examine the influence of polymorphism in alpha 3 on cytolytic T-cell recognition of naturally occurring class I antigens.
供体OZB表达的HLA - A2抗原可通过等电聚焦与主要的HLA - A2.1亚型区分开来——它的酸性多一个电荷单位——并且可被一些同种异体反应性T细胞克隆识别，但不能被细胞溶解T淋巴细胞系识别。已通过与A2.1进行比较肽图谱分析和放射化学序列分析来研究变体OZB的结构。发现这两种分子在α3区域的一个胰蛋白酶肽段上存在差异，该肽段跨越第220 - 243位氨基酸残基。来自变体OZB的该肽段的氨基酸序列显示，在第236位氨基酸处只有一个氨基酸变化，即谷氨酸取代了丙氨酸，这是I类HLA抗原中一个迄今不变的残基。所有先前已鉴定的HLA或H - 2天然变体的结构变化都局限于α1和/或α2结构域。因此，变体OZB的独特之处在于：（1）它在α3区域有一个氨基酸变化；（2）它在α1和α2区域没有变化。该变体唯一检测到的替换可能是由DNA水平的单个碱基变化引起的，这表明它可能是由A2.1基因中的点突变导致的。变体OZB的结构特征为研究α3区域多态性对天然存在的I类抗原的细胞溶解T细胞识别的影响开辟了一条新途径。
