Gustafsson K, LeGuern C, Hirsch F, Germana S, Pratt K, Sachs D H
Transplantation Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1990 Sep 15;145(6):1946-51.
Two cDNA clones coding for allelic miniature swine MHC class II Ag DQB chains have been isolated, characterized, and shown to be expressed after transfection into mouse fibroblasts. The two alleles differ at the nucleotide level by an overwhelming proportion of replacement substitutions, suggesting the influence of selection for polymorphism. Most of the resulting predicted amino acid replacements are in regions commonly polymorphic in mouse Ab and human DQB sequences, corresponding to the predicted Ag recognition site. Nucleotide and amino acid sequence comparisons to homologous mouse and human sequences show more similarity between swine and man than between either swine and mouse or man and mouse. This tendency is most pronounced when comparing the 3' untranslated regions. However, an examination of unique cross-species sharing of amino acid residues suggests a closer relationship between both man and miniature swine and man and mouse than between miniature swine and mouse. The simplest explanation we can envision for these findings is that the mouse DQB gene homologue (Ab) has been subject to a higher substitution rate than either swine or human DQB genes. An additional cytoplasmic exon expressed in mouse Ab gene products and in putative human DQB2 gene products is lacking in both swine and human DQB cDNA clones. Its absence suggests either that the expression of this exon in mouse Ab genes was activated after mammalian speciation or that the expression of this exon was independently inactivated in swine DQB and human DQB1 genes. Alternatively, the mouse Ab gene may be derived from the same primordial gene as human DQB2, whereas the pig DQB gene may be derived from the same primordial gene as the human DQB1 gene.
已分离、鉴定出两个编码等位基因小型猪MHCⅡ类抗原DQB链的cDNA克隆，并证明它们在转染到小鼠成纤维细胞后能够表达。这两个等位基因在核苷酸水平上存在大量的替换性替代差异，表明存在多态性选择的影响。由此产生的大多数预测氨基酸替代位于小鼠抗体和人类DQB序列中常见的多态性区域，对应于预测的抗原识别位点。与同源小鼠和人类序列的核苷酸和氨基酸序列比较表明，猪与人之间的相似性高于猪与小鼠或人与小鼠之间的相似性。在比较3'非翻译区时，这种趋势最为明显。然而，对独特的跨物种氨基酸残基共享情况的研究表明，人与小型猪以及人与小鼠之间的关系比小型猪与小鼠之间的关系更为密切。我们能为这些发现设想的最简单解释是，小鼠DQB基因同源物（抗体）的替换率高于猪或人类的DQB基因。在猪和人类DQB cDNA克隆中均缺乏在小鼠抗体基因产物和推定的人类DQB2基因产物中表达的一个额外的胞质外显子。它的缺失表明，要么该外显子在小鼠抗体基因中的表达是在哺乳动物物种形成后被激活的，要么该外显子在猪DQB和人类DQB1基因中独立失活。或者，小鼠抗体基因可能与人类DQB2来自同一个原始基因，而猪DQB基因可能与人类DQB1基因来自同一个原始基因。
