The inter-locus recombinant HLA-B*4601 has high selectivity in peptide binding and functions characteristic of HLA-C
The inter-locus recombinant HLA-B*4601 has high selectivity in peptide binding and functions characteristic of HLA-C
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DOI：
10.1084/jem.184.2.735
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发表时间：
1996-08-01
影响因子：
15.3
通讯作者：
Parham, P
中科院分区：
文献类型：
--
作者：
Barber, LD;Percival, L;Parham, P
绝大多数新的人类HLA I类等位基因是由同一位点的现有等位基因之间的转换形成的。一个值得注意的例外是HLA-B*4601，它是由Cw*0102的同源片段取代B*1501的α 1螺旋的66-76残基形成的。这种基因座间重组，将HLA-B和HLA-C结构的特征元素聚集在一起，在这里显示出对功能的显著影响。B*4601结合的天然加工肽不同于亲本异型B*1501和Cw*0102，由3个高丰度肽主导。B*4601增加的肽选择性在HLA-A、B、C等位型中是独一无二的。在其他功能方面，在HLA-B框架中存在一小段hla - c衍生序列可将B*4601转化为hla - c样分子。同种反应性细胞毒性T淋巴细胞（CTL）、自然杀伤细胞（NK）和细胞糖苷酶都能识别B*4601，就像它是HLA-C同种异体一样。这些不寻常的特性是一种在东南亚人群中频率高达20%的同种异型，并与自身免疫性疾病和鼻咽癌的易感性相关。
The vast majority of new human HLA class I alleles are formed by conversions between existing alleles of the same locus. A notable exception to this rule is HLA-B*4601 formed by replacement of residues 66-76 of the alpha 1 helix of B*1501 by the homologous segment of Cw*0102. This inter-locus recombination, which brings together characteristic elements of HLA-B and HLA-C structure, is shown here to influence function dramatically. Naturally processed peptides bound by B*4601 are distinct from those of its parental allotypes B*1501 and Cw*0102 and dominated by three high abundance peptides. Such increased peptide selectivity by B*4601 is unique among HLA-A,B,C allotypes. For other aspects of function, presence of the small segment of HLA-C-derived sequence in an otherwise HLA-B framework converts B*4601 to an HLA-C-like molecule. Alloreactive cytotoxic T lymphocytes (CTL), natural killer (NK) cells, and cellular glycosidases all recognize B*4601 as though it were an HLA-C allotype. These unusual properties are those of an allotype which has frequencies as high as 20% in south east Asian populations and is associated which predisposition to autoimmune diseases and nasopharyngeal carcinoma.