Berstein R M, Schluter S F, Shen S, Marchalonis J J
University of Arizona, Department of Microbiology and Immunology, College of Medicine, Tucson, 85724, USA.
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3289-93. doi: 10.1073/pnas.93.8.3289.
All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution.
在整个系统发育过程中，所有免疫球蛋白和T细胞受体都共享高度保守的氨基酸序列区域。为了鉴定可能的原始免疫球蛋白和免疫球蛋白样分子，我们利用3' RACE（cDNA末端快速扩增）和高度保守的恒定区共有氨基酸序列，从沙虎鲨（Carcharhinus plumbeus）中分离出一种新的免疫球蛋白类别。这种免疫球蛋白称为IgW，其分泌形式由782个氨基酸组成，在胸腺和脾脏中均有表达。该分子总体上与鳐鱼和人类的μ链以及从护士鲨中分离出的一种新的推定抗原结合分子（NAR）最为相似。全长IgW链具有类似于人类和鲨鱼重链（VH）序列的可变区，以及一个包含H链特有的WGXGT基序的新型连接段。然而，与任何其他H链型分子不同的是，它包含六个恒定（C）结构域。第一个C结构域包含Cμ1特有的半胱氨酸残基，可与轻链（L）二聚化。第四和第六个结构域也含有类似的半胱氨酸，可与其他H链二聚化或形成同型二聚体。IgW V结构域和C结构域序列的比较显示，其同源性高于VH与Cμ或VL与CL之间比较所发现的同源性，从而表明IgW可能在进化过程中保留了原始免疫球蛋白的特征。
