Chintalacharuvu K R, Raines M, Morrison S L
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.
J Immunol. 1994 Jun 1;152(11):5299-304.
IgA is the major Ig synthesized in humans and provides the first line of defense at the mucosal surfaces. The constant region of IgA heavy chain is encoded by the alpha gene on chromosome 14. Previous studies have indicated the presence of two alpha genes, alpha 1 and alpha 2, with alpha 2 existing in two allotypic forms, alpha 2 m(1) and alpha 2 m(2). Here we report the cloning and complete nucleotide sequence determination of a novel human alpha gene. Nucleotide sequence comparison with the published alpha sequences suggests that the gene arose as a consequence of recombination or gene conversion between the two alpha 2 alleles. We have expressed the gene as a chimeric protein in myeloma cells indicating that it encodes a functional protein. The novel IgA resembles IgA2 m(2) in that disulfide bonds link H and L chains. This novel recombinant gene provides insights into the mechanisms of generation of different constant regions and suggests that within human populations, multiple alleles of alpha may be present providing IgAs of different structures.
IgA是人类合成的主要免疫球蛋白，在黏膜表面提供第一道防线。IgA重链的恒定区由14号染色体上的α基因编码。先前的研究表明存在两个α基因，即α1和α2，其中α2以两种同种异型形式存在，即α2m(1)和α2m(2)。在此我们报告一个新型人类α基因的克隆及完整核苷酸序列测定。与已发表的α序列进行核苷酸序列比较表明，该基因是两个α2等位基因之间重组或基因转换的结果。我们已在骨髓瘤细胞中将该基因表达为嵌合蛋白，表明它编码一种功能性蛋白。这种新型IgA类似于IgA2m(2)，因为二硫键连接重链和轻链。这个新型重组基因有助于深入了解不同恒定区产生的机制，并表明在人类群体中可能存在多个α等位基因，从而产生不同结构的IgA。
