Department of Microbiology and Immunology, University of Maryland Baltimore, Baltimore, MD, 21201, USA.
Centro de Investigacão Em Biodiversidade E Recursos Genéticos, CIBIO-InBIO, Campus Agrário de Vairão, Universidade Do Porto, Vairão, Porto, Portugal.
Immunogenetics. 2021 Aug;73(4):333-348. doi: 10.1007/s00251-021-01209-6. Epub 2021 Mar 19.
Natural killer (NK) cells play major roles in innate immunity against viruses and cancer. Natural killer receptors (NKR) expressed by NK cells recognize foreign- or self-ligands on infected and transformed cells as well as healthy cells. NKR genes are the most rapidly evolving loci in vertebrates, and it is generally difficult to detect orthologues in different taxa. The unique exception is NKp30, an activating NKR in mammals that binds to the self-ligand B7H6. The NKp30-encoding gene, NCR3, has been found in most vertebrates including sharks, the oldest vertebrates with human-type adaptive immunity. NCR3 has a special, non-rearranging VJ-type immunoglobulin superfamily (IgSF) domain that predates the emergence of the rearranging antigen receptors. Herein we show that NCR3 loci are linked to the shark major histocompatibility complex (MHC), proving NCR3's primordial association with the MHC. We identified eight subtypes of differentially expressed highly divergent shark NCR3 family genes. Using in situ hybridization, we detected one subtype, NS344823, to be expressed by predominantly single cells outside of splenic B cell zones. The expression by non-B cells was also confirmed by PCR in peripheral blood lymphocytes. Surprisingly, high expression of NS344823 was detected in the thymic cortex, demonstrating NS344823 expression in developing T cells. Finally, we show for the first time that shark T cells are found as single cells or in small clusters in the splenic red pulp, also unassociated with the large B cell follicles we previously identified.
自然杀伤 (NK) 细胞在抗病毒和抗癌的先天免疫中发挥主要作用。NK 细胞表达的自然杀伤受体 (NKR) 识别感染和转化细胞以及健康细胞上的外来或自身配体。NKR 基因是脊椎动物中进化最快的基因座，通常很难在不同分类群中检测到同源物。唯一的例外是 NKp30，一种在哺乳动物中起激活作用的 NKR，可与自身配体 B7H6 结合。NKp30 编码基因 NCR3 已在包括鲨鱼在内的大多数脊椎动物中发现，鲨鱼是具有人类型适应性免疫的最古老脊椎动物。NCR3 具有特殊的、非重排的免疫球蛋白超家族 (IgSF) 结构域，该结构域早于重排抗原受体的出现。本文中，我们证明了 NCR3 基因座与鲨鱼主要组织相容性复合体 (MHC) 相关，证明了 NCR3 与 MHC 的原始关联。我们鉴定了 8 种不同表达的高度分化的鲨鱼 NCR3 家族基因亚型。通过原位杂交，我们检测到一个亚型 NS344823 主要由脾脏 B 细胞区外的单个细胞表达。外周血淋巴细胞的 PCR 也证实了非 B 细胞的表达。令人惊讶的是，在胸腺皮质中检测到 NS344823 的高表达，表明 NS344823 在发育中的 T 细胞中表达。最后，我们首次证明鲨鱼 T 细胞以单个细胞或小细胞簇的形式存在于脾脏红髓中，也与我们之前鉴定的大 B 细胞滤泡无关。
