Gaur Lakshmi K, Heise Eugene R, Clark Edward A
Department of Microbiology and Immunology, Bowman Gray School of Medicine, Winston-Salem, North Carolina.
Washington Regional Primate Research Center, Seattle.
Am J Primatol. 1990;21(1):31-40. doi: 10.1002/ajp.1350210104.
The reactivity of a panel of 40 monoclonal antibodies (mAb) specific for HLA class I antigens was assessed in 117 unrelated Macaca mulatta (Mm), with a standard microcytotoxicity assay, in order to compare phenotypic frequencies with those previously reported for M. fascicularis (Mfl) and M. nemestrina (Mn). Based on the reactivity with HLA typed human cell panels, the epitopes recognized by these mAb in macaques were classified as nonpolymorphic, polymorphic "public," and polymorphic "private." Nei's genetic identity (I) and distance (D) formulae were applied to estimate I and D between each of the macaque species and between each macaque species and humans. The HLA nonpolymorphic epitopes emerged as spcies-specific determinants, as all three macaque species showed clear differences from each other and from humans in the frequency of occurrence in population samples. From our previous serologic study and from published sequence data, it is evident that the major histocompatibility complex (MHC) is highly conserved in primate evolution. Ninety percent of the mAb reacted at a similar frequency in either two or three macaque species. With few exceptions, the mAb reacted at a greater frequency in humans than in macaques. Concerning private HLA class I epitopes, we have previously speculated that the human MHC class I polymorphisms probably predate the diversification of macaque-human lineages, and hence would be highly conserved. However, the inconsistent pattern of occurrence of human monomorphic epitopes among the macaque species suggests that a complex explanation is required. One possibility is that HLA monomorphic epitopes are invariant in humans because of their yet unknown functional role; however, this explanation loses some force because of the inconsistent pattern of occurrence among three closely related species of Macaca. However, we favor a second possibility, i.e., that the monomorphic epitopes in humans might be the result of the accumulated neutral mutations and are not subjected to functional constraints. This explanation seems to fit the inconsistent pattern of occurrence of these epitopes among macaques.
采用标准微量细胞毒性试验，评估了针对HLA I类抗原的40种单克隆抗体（mAb）对117只无亲缘关系的食蟹猴（Mm）的反应性，以便将表型频率与先前报道的束尾猴（Mfl）和豚尾猴（Mn）的表型频率进行比较。根据与HLA分型的人类细胞板的反应性，这些mAb在猕猴中识别的表位被分类为非多态性、多态性“公共”和多态性“私有”。应用内氏遗传同一性（I）和距离（D）公式来估计每只猕猴物种之间以及每只猕猴物种与人类之间的I和D。HLA非多态性表位成为物种特异性决定因素，因为在群体样本中，所有三种猕猴物种彼此之间以及与人类在出现频率上都表现出明显差异。从我们之前的血清学研究和已发表的序列数据来看，主要组织相容性复合体（MHC）在灵长类进化中高度保守。90%的mAb在两种或三种猕猴物种中的反应频率相似。除少数例外，mAb在人类中的反应频率高于猕猴。关于私有HLA I类表位，我们之前推测人类MHC I类多态性可能早于猕猴 - 人类谱系的分化，因此会高度保守。然而，人类单态性表位在猕猴物种中的出现模式不一致，这表明需要一个复杂的解释。一种可能性是，HLA单态性表位在人类中是不变的，因为它们尚未知的功能作用；然而，由于在三种密切相关的猕猴物种中出现模式不一致，这种解释的说服力有所减弱。不过，我们倾向于第二种可能性，即人类中的单态性表位可能是累积中性突变的结果，并且不受功能限制。这种解释似乎符合这些表位在猕猴中出现的不一致模式。
