Suppression of H-2b-associated resistance to Friend erythroleukemia virus by a class I gene from the H-2d major histocompatibility complex haplotype.
Suppression of H-2b-associated resistance to Friend erythroleukemia virus by a class I gene from the H-2d major histocompatibility complex haplotype.
复制标题
H-2d 主要组织相容性复合体单倍型的 I 类基因抑制 H-2b 相关的对 Friend 红白血病病毒的耐药性。
DOI：
10.1073/pnas.88.20.9243
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发表时间：
1991
影响因子：
11.1
通讯作者：
Lilly,F
中科院分区：
文献类型：
--
作者：
Polsky,D;Lilly,F
在主要组织相容性复合体上具有H-2d单倍型纯合子的小鼠明显比具有H-2b单倍型纯合子的同源小鼠更容易被Friend小鼠白血病逆转录病毒（FV）分离物诱导红白血病。H-2b单倍型赋予的抗性在这个杂交中是隐性的，因为杂合子F1小鼠和亲本菌株H-2d纯合子一样易感。然而，H-2b相关的抗性并不是一种内在的隐性性状，因为H-2b/H-2dm1杂合子在对FV的相对抗性方面与H-2b纯合子相似；突变体H-2dm1单倍型缺少亲本单倍型的整个D区，除了末端D区基因融合形成一个I类基因，产生一个与亲本基因不同的I类基因，因此这一发现表明H-2d单倍型的一个或多个D区基因可以积极抑制h -2b相关抗性。与H-2dm1不同，突变体H-2dm2单倍型在H-2d单倍型的D区仅保留IDd类基因，强烈抑制H-2b/H-2dm2杂合子的抗性，Dd作为转基因的存在显著降低H-2b纯合子的抗性。由于H-2b对FV的相关抗性似乎主要是由于Lb（也称为Db）的能力，Lb是H-2b单倍型D区唯一编码的I类分子，可以呈现病毒表位以供FV特异性细胞毒性T淋巴细胞识别。Dd分子对FV抗性的抑制表明，主要组织相容性复合体的一类分子的存在可以干扰另一类分子对病毒表位的呈现，也可以干扰识别所呈现病毒表位的T细胞的产生。
Mice homozygous for the H-2d haplotype at the major histocompatibility complex are markedly more susceptible to erythroleukemia induction by the Friend isolate of murine leukemia retrovirus (FV) than are congenic mice homozygous for the H-2b haplotype. The resistance conferred by the H-2b haplotype is recessive in this cross, since heterozygous F1 mice are as susceptible as parental strain H-2d homozygotes. However, H-2b-associated resistance is not an intrinsically recessive trait, since H-2b/H-2dm1 heterozygotes resemble H-2b homozygotes in their relative resistance to FV; the mutant H-2dm1 haplotype lacks the entire D region of the parental haplotype except for a single class I gene formed by the fusion of its terminal D-region genes to produce a class I gene differing from both parental genes, and thus this finding indicates that one or more D-region genes of the H-2d haplotype can actively suppress H-2b-associated resistance. Unlike H-2dm1, the mutant H-2dm2 haplotype, which retains only the class IDd gene in the D region of the H-2d haplotype, strongly suppresses resistance in H-2b/H-2dm2 heterozygotes, and the presence of Dd as a transgene significantly reduces the resistance of H-2b homozygotes. Since H-2b-associated resistance to FV appears to be due mainly to the capacity of Lb (also called Db), the only class I molecule encoded in the D region of the H-2b haplotype, to present viral epitopes for recognition by FV-specific cytotoxic T lymphocytes, suppression of resistance to FV by the Dd molecule implies that the presence of one class I molecule of the major histocompatibility complex can interfere with either the presentation of viral epitopes by another class I molecule or the generation of T cells that recognize viral epitopes so presented.