Bondinas George P, Moustakas Antonis K, Papadopoulos George K
Laboratory of Biochemistry and Biophysics, Faculty of Agricultural Technology, Epirus Institute of Technology, GR47100 Arta, Greece.
Immunogenetics. 2007 Jul;59(7):539-53. doi: 10.1007/s00251-007-0224-8. Epub 2007 May 12.
The list of alleles in the HLA-DRB, HLA-DQA, and HLA-DQB gene loci has grown enormously since the last listing in this journal 8 years ago. Crystal structure determination of several human and mouse HLA class II alleles, representative of two gene loci in each species, enables a direct comparison of ortholog and paralog loci. A new numbering system is suggested, extending earlier suggestions by [Fremont et al. in Immunity 8:305-317, (1998)], which will bring in line all the structural features of various gene loci, regardless of animal species. This system allows for structural equivalence of residues from different gene loci. The listing also highlights all amino acid residues participating in the various functions of these molecules, from antigenic peptide binding to homodimer formation, CD4 binding, membrane anchoring, and cytoplasmic signal transduction, indicative of the variety of functions of these molecules. It is remarkable that despite the enormous number of unique alleles listed thus far (DQA = 22, DQB = 54, DRA = 2, and DRB = 409), there is invariance at many specific positions in man, but slightly less so in mouse or rat, despite their much lower number of alleles at each gene locus in the latter two species. Certain key polymorphisms (from substitutions to an eight-residue insertion in the cytoplasmic tail of certain DQB alleles) that have thus far gone unnoticed are highly suggestive of differences or diversities in function and thus call for further investigation into the properties of these specific alleles. This listing is amenable to supplementation by future additions of new alleles and the highlighting of new functions to be discovered, providing thus a unifying platform of reference in all animal species for the MHC class II allelic counterparts, aiding research in the field and furthering our understanding of the functions of these molecules.
自8年前本期刊上一次列出HLA - DRB、HLA - DQA和HLA - DQB基因座中的等位基因列表以来，其数量已大幅增加。对几种人类和小鼠HLA II类等位基因（分别代表每个物种的两个基因座）进行晶体结构测定，能够对直系同源基因座和旁系同源基因座进行直接比较。本文提出了一种新的编号系统，扩展了[弗里蒙特等人发表于《免疫》8:305 - 317，(1998)]的早期建议，该系统将使不同基因座的所有结构特征保持一致，而不论动物物种如何。该系统允许不同基因座的残基具有结构等效性。该列表还突出显示了参与这些分子各种功能的所有氨基酸残基，从抗原肽结合到同二聚体形成、CD4结合、膜锚定和细胞质信号转导，表明了这些分子功能的多样性。值得注意的是，尽管到目前为止列出了大量独特的等位基因（DQA = 22，DQB = 54，DRA = 2，DRB = 409），但人类许多特定位置存在不变性，而在小鼠或大鼠中这种不变性稍少，尽管后两个物种每个基因座的等位基因数量要少得多。某些迄今未被注意到的关键多态性（从某些DQB等位基因细胞质尾巴中的替换到八残基插入）强烈暗示了功能上的差异或多样性，因此需要进一步研究这些特定等位基因的特性。该列表便于未来补充新的等位基因并突出显示有待发现的新功能，从而为所有动物物种的MHC II类等位基因对应物提供一个统一的参考平台，有助于该领域的研究并加深我们对这些分子功能的理解。
