Foo-Phillips M, Kozak C A, Principato M A, Abe R
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1992 Dec 1;149(11):3440-7.
The genetic linkage of loci encoding stimulatory Mlsa and Mlsc determinants with proviruses of mouse mammary tumour viruses (MMTV) has been shown. We previously have reported that the ligand(s) for V beta 5, V beta 11, and V beta 12 behaves as a novel minor lymphocyte-stimulating (Mls) determinant(s), Mlsf, to induce the strong proliferation of unprimed T cells, and that this ligand(s) also functions as a self-Ag for the clonal deletion of self-reactive T cells. In the accompanying paper (Part I), a unique polymorphism characteristic of the Mlsf gene product is presented. In order to determine the genetic basis for this novel Mls system, we examined the progeny of multiple genetic crosses to identify the MMTV proviral loci involved in the clonal deletion of self-Mlsf-reactive T cells. Results from these investigations indicated that at least three known MMTV proviruses, Mtv-8, Mtv-9, and Mtv-11 are involved in the expression of Mlsf gene products. Presence of Mtv-9 results in the complete deletion of V beta 5, V beta 11, and V beta 12; Mtv-8 is associated with the complete deletion of V beta 12, but only a partial deletion of V beta 11 (primarily CD4-positive T cell subset) with little or no deletion of V beta 5; and Mtv-11 induces the complete deletion of V beta 11 and V beta 12, but no deletion of V beta 5. Given the significant sequence homology in the C-terminal portion of the open reading frame (ORF) region among these three MMTV and the almost equivalent effect of these three MMTV provirus upon the V beta 12 repertoire, their apparent hierarchic effect upon the V beta 5 and V beta 11 repertoires suggests that affinity differences in recognition of the same determinant by different TCR V beta may play a significant role in the clonal deletion of self-reactive T cells.
已证明编码刺激性Mlsa和Mlsc决定簇的基因座与小鼠乳腺肿瘤病毒（MMTV）的前病毒存在遗传连锁。我们之前曾报道，Vβ5、Vβ11和Vβ12的配体表现为一种新型的次要淋巴细胞刺激（Mls）决定簇Mlsf，可诱导未致敏T细胞的强烈增殖，并且该配体还作为自身抗原参与自身反应性T细胞的克隆清除。在随附论文（第一部分）中，展示了Mlsf基因产物独特的多态性特征。为了确定这个新型Mls系统的遗传基础，我们检测了多个遗传杂交的后代，以鉴定参与自身Mlsf反应性T细胞克隆清除的MMTV前病毒基因座。这些研究结果表明，至少三种已知的MMTV前病毒Mtv - 8、Mtv - 9和Mtv - 11参与了Mlsf基因产物的表达。Mtv - 9的存在会导致Vβ5、Vβ11和Vβ12完全缺失；Mtv - 8与Vβ12的完全缺失相关，但仅导致Vβ11部分缺失（主要是CD4阳性T细胞亚群），而Vβ5几乎没有或没有缺失；Mtv - 11会诱导Vβ11和Vβ12完全缺失，但Vβ5不缺失。鉴于这三种MMTV在开放阅读框（ORF）区域的C末端部分存在显著的序列同源性，并且这三种MMTV前病毒对Vβ12库的影响几乎相同，它们对Vβ5和Vβ11库的明显层次效应表明，不同TCR Vβ对相同决定簇识别的亲和力差异可能在自身反应性T细胞的克隆清除中起重要作用。
