EVOLUTION OF HLA ANTIGENIC DETERMINANTS - SPECIES CROSS-REACTIONS OF MONOCLONAL-ANTIBODIES

EVOLUTION OF HLA ANTIGENIC DETERMINANTS - SPECIES CROSS-REACTIONS OF MONOCLONAL-ANTIBODIES
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DOI:
10.1007/bf00621948
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发表时间:
1982-01-01
期刊:
影响因子:
3.2
通讯作者:
PARHAM, P
PARHAM, P
中科院分区:
医学4区
文献类型:
--
作者:
BRODSKY, FM;PARHAM, P

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用小鼠HLA-A-、-B-、-C单克隆抗体对50个种细胞的反应进行了研究。通过结合测定进行分析。在人类中是单态的抗体通常在其他物种中显示单态行为,并且观察到许多显著的交叉反应。识别高度特异性多态性决定簇的抗体与其他物种几乎没有交叉反应。在人类中识别广泛多态性决定簇的抗体以多态性方式与许多其他物种交叉反应。单态和广泛多态性的决定因素的交叉反应模式大致与目前的系统发育关系的图片。有两种根本不同的多态性决定簇,一种在进化中相对保守,另一种是最近变化的产物。它们可能与小鼠H-2抗原的公共抗原和私人抗原有关。HLA-A、-B、-C基因的一个简单遗传模型,即一个基因座上的所有特异性都是真正的等位基因,足以解释这些交叉反应模式。以前看到的交叉反应与同种抗血清可能是由于广泛的多态性抗体,而不是等位基因特异性抗体。如果是这样的话,那么就没有实验基础来证明博德默的MHC(主要组织相容性复合体)多态性模型是由于控制了串联基因阵列的表达。
The reactions of mouse monoclonal HLA-A-, -B-, -C-specific antibodies on cells from 50 spp. were analyzed by binding assay. Antibodies which are monomorphic in humans generally show monomorphic behavior in other species and many significant cross-reactions were seen. Antibodies which recognize highly specific polymorphic determinants gave few cross-reactions with other species. Antibodies which recognize broad polymorphic determinants in humans cross-reacted in a polymorphic manner with many other species. The patterns of cross-reaction for both monomorphic and broadly polymorphic determinants correlated roughly with the current picture of phylogenetic relationships. There are 2 fundamentally different classes of polymorphic determinants, one which appears relatively conserved in evolution and one which is the product of recent change. They probably correlate with the public and private antigens of mouse H-2 antigens. A simple genetic model of HLA-A, -B, -C genes, whereby all specificities at a locus are true alleles, is sufficient to explain these patterns of cross-reaction. Cross-reactions previously seen with alloantisera were probably due to broadly polymorphic antibodies rather than to allele-specific antibodies. If this were the case, then no experimental basis for Bodmer''s model of MHC [major histocompatibility complex] polymorphism being due to control of expression of a tandem array of genes exists.