MHC class I molecule-restricted presentation of viral antigen in beta 2-microglobulin-deficient mice.
MHC class I molecule-restricted presentation of viral antigen in beta 2-microglobulin-deficient mice.
复制标题
β2-微球蛋白缺陷小鼠中 MHC I 类分子限制性病毒抗原呈递。
作者：
F. Lehmann;H. Dralle;O. Utermöhlen;J. Löhler
通常，Ag 作为三联复合物呈递给 CD8+ T 淋巴细胞，该三联复合物由肽表位、MHC 编码的 I 类重 (α) 链和 β 2-微球蛋白 (β 2-m) 轻链组成。尽管对于肽和 α 链的功能已达成共识，但 β 2-m 的作用仍不确定。特别是，如果没有Ag的参与，Ag是否可以被呈现？我们试图通过使用β2-m基因已被同源重组破坏的小鼠来获得答案。结果，没有轻链被合成，而且，即使有也很少形成CD8+T淋巴细胞。从急性感染小鼠的组织中清除淋巴细胞性脉络膜脑膜炎 (LCM) 病毒仅由 CD8+ T 淋巴细胞介导；因此，在缺乏β2-m的突变体中，感染无法终止。这里显示，输注来自同基因β2-m+/+小鼠和MHC K或D相容小鼠的免疫脾细胞导致病毒清除。与野生型小鼠相比，β 2-m 缺陷型小鼠需要大约五倍的细胞才能达到抗病毒效果，但通过用 IFN-γ 或 β 2-m 治疗前者来改善消除效果的尝试失败了。消除免疫脾细胞中的 CD8+ T 淋巴细胞，但不消除 CD4+ T 淋巴细胞，从而消除了抗病毒潜力。我们得出的结论是，尽管完全不存在 β2-m，但感染 LCM 病毒的小鼠细胞仍可以将病毒 Ag 与 I 类 MHC 分子 K 和 D 一起呈递给 CD8+ 效应 T 淋巴细胞。
Normally, Ag is presented to CD8+ T lymphocytes as a tripartite complex consisting of peptide epitope, MHC-encoded class I heavy (alpha) chain, and beta 2-microglobulin (beta 2-m) light chain. Although there is agreement about the function of both peptide and alpha-chain, the role of beta 2-m has remained uncertain. In particular, can Ag be presented without its participation? We have sought to obtain an answer by using mice in which the gene for beta 2-m had been disrupted by homologous recombination. As a consequence, no light chains are synthesized and, furthermore, few if any CD8+ T lymphocytes are formed. Elimination of lymphocytic choriomeningitis (LCM) virus from the tissues of acutely infected mice is mediated solely by CD8+ T lymphocytes; hence, in the beta 2-m-lacking mutants the infection cannot be terminated. Here it is shown that infusion of immune spleen cells from syngeneic beta 2-m+/+ mice and from mice compatible in K or D of the MHC resulted in virus clearance. Approximately five times more cells were required to achieve antiviral effects in beta 2-m-deficient than in wild-type mice but attempts to improve elimination by treatment of the former with IFN-gamma or beta 2-m have failed. Depleting the immune splenocytes of CD8+ T lymphocytes but not of CD4+ T lymphocytes abolished the antiviral potential. We conclude that LCM virus-infected murine cells can present viral Ag to CD8+ effector T lymphocytes together with class I MHC molecules K and D, despite the total absence of beta 2-m.