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PMID: 2251255 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Resolution of hypervariable regions in T-cell receptor beta chains by a modified Wu-Kabat index of amino acid diversity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 23 ·1990-12-00 ·Pages 9138-42

Jores R, Alzari PM, Meo T

Abstract

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.

MeSH Terms
Amino Acid Sequence Genes, Immunoglobulin Genetic Variation Immunoglobulin Fab Fragments Immunoglobulin Variable Region/genetics Macromolecular Substances Models, Molecular Multigene Family Protein Conformation Receptors, Antigen, T-Cell/genetics
Chemicals
Immunoglobulin Fab Fragments Immunoglobulin Variable Region Macromolecular Substances Receptors, Antigen, T-Cell
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Jores R
Unité d'Immunogénétique, Insitut National de la Santé et de la Recherche Médicale, Institut Pasteur, Paris, France.
Alzari P M
Meo T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.23.9138
Published
1990-12-00
Pages
9138-42
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC55119
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.87.23.9138 PMC Full Text View journal details
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