Liu J, Morris M A, Nguyen P, George T C, Koulich E, Lai W C, Schatzle J D, Kumar V, Bennett M
Department of Pathology, Laboratory of Molecular Pathology, Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
J Immunol. 2000 Feb 15;164(4):1793-9. doi: 10.4049/jimmunol.164.4.1793.
The Ly49 family of genes encode NK cell receptors that bind class I MHC Ags and transmit negative signals if the cytoplasmic domains have immunoregulatory tyrosine-based inhibitory motifs (ITIMs). 5E6 mAbs recognize Ly49C and Ly49I receptors and depletion of 5E6+ NK cells prevents rejection of allogeneic or parental-strain H2d bone marrow cell (BMC) grafts. To determine the function of the Ly49I gene in the rejection of BMC grafts, we transfected fertilized eggs of FVB mice with a vector containing DNA for B6 strain Ly49I (Ly49IB6). Ly49IB6 is ITIM+ and is recognized by 5E6 as well as Ly49I-specific 8H7 mAbs. Normal FVB H2q mice reject H2b but not H2d BMC allografts, and the rejection of H2b BMC was inhibited partially by anti-NK1.1 and completely by anti-asialo GM1, but not by anti-CD8, Abs. In FVB mice, NK1.1 is expressed on only 60% NK cells. FVB. Ly49IB6 hosts failed to reject H2d or H2b BMC, but did reject class I-deficient TAP-1-/- BMC, indicating that NK cells were functional. Nondepleting doses of anti-Ly49I Abs reversed the acceptance of H2b BMC by FVB.Ly49IB6 mice. FVB.Ly49IB6+/- mice were crossed and back-crossed with 129 mice-H2b, 5E6-, poor responders to H2d BMC grafts. While transgene-negative H2b/q F1 or first-generation back-crossed mice rejected H2b marrow grafts (hybrid resistance), transgene-positive mice did not. Thus B6 strain Ly49I receptors transmit inhibitory signals from H2b MHC class I molecules. Moreover, Ly49IB6 has no positive influence on the rejection of H2d allografts.
Ly49基因家族编码自然杀伤（NK）细胞受体，这些受体可结合I类主要组织相容性复合体（MHC）抗原，若其胞质结构域含有基于免疫调节酪氨酸的抑制基序（ITIMs），则可传递负性信号。5E6单克隆抗体（mAbs）可识别Ly49C和Ly49I受体，清除5E6 + NK细胞可防止同种异体或亲本品系H2d骨髓细胞（BMC）移植被排斥。为确定Ly49I基因在BMC移植排斥中的功能，我们用含有B6品系Ly49I（Ly49IB6）DNA的载体转染FVB小鼠的受精卵。Ly49IB6含有ITIM，可被5E6以及Ly49I特异性的8H7 mAbs识别。正常FVB H2q小鼠可排斥H2b但不排斥H2d BMC同种异体移植，H2b BMC的排斥反应可被抗NK1.1部分抑制，被抗去唾液酸GM1完全抑制，但不被抗CD8抗体抑制。在FVB小鼠中，只有60%的NK细胞表达NK1.1。FVB.Ly49IB6宿主无法排斥H2d或H2b BMC，但可排斥I类缺陷的TAP-1 - / - BMC，这表明NK细胞具有功能。非清除剂量的抗Ly49I抗体可逆转FVB.Ly49IB6小鼠对H2b BMC的接受。FVB.Ly49IB6 +/- 小鼠与129小鼠-H2b、5E6 - （对H2d BMC移植反应较差）进行杂交和回交。虽然转基因阴性的H2b/q F1或第一代回交小鼠可排斥H2b骨髓移植（杂种抗性），但转基因阳性小鼠则不能。因此，B6品系Ly49I受体可从H2b MHC I类分子传递抑制性信号。此外，Ly49IB6对H2d同种异体移植的排斥没有正向影响。
