期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1990
卷号:87
期号:23
页码:9138-9142
DOI:10.1073/pnas.87.23.9138
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:The Wu-Kabat variability coefficient is a well-established descriptor of the susceptibility of an amino acid position to evolutionary replacements. It conveniently highlights stretches of accentuated amino acid variation that, for example, in an antibody molecule account for most of the antigen contacts (complementarity-determining regions). Diverse opinion are held as to why the index yields unclear results when applied instead to the polypeptide sequences of the T-cell antigen receptor. We show that a simple modification enhances the resolving power of the index by increasing the weight on the frequency distribution of the amino acids in the formula. Application of the improved index to T-cell receptor beta chains highlights four unambiguous hypervariable regions, three of which are positioned similar to immunoglobulin complementarity-determining regions along the chain. In a Fab-like three-dimensional model of the T-cell receptor, the four hypervariable regions coincide with the four loops on the surface of the domain and form a contiguous area available for binding.