TY - JOUR
T1 - A Shannon entropy analysis of immunoglobulin and T cell receptor
AU - Stewart, Jeffrey J.
AU - Lee, Connie Y.
AU - Ibrahim, Saleh
AU - Watts, Perry
AU - Shlomchik, Mark
AU - Weigert, Martin
AU - Litwin, Samuel
N1 - Funding Information:
Kabat's prediction that highly variable immunoglobulin (Ig) sites contact antigen (Kabat, 1970) has since been verified by antigen-bound Ig crystal structures (Mac- a Dedicated to the memory of Tommaso Meo who inspired this study and so many others. * This publication was supported by grants from the NIH R37 GM-20964 and NIAID ROI AI34882 and by the Sheryl N. Hirsch Award from the Lupus Foundation of Philadelphia. t These two authors contributed equally to this work. §Current address: University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103 II Current address: Institut fUr Immunologie, Rostock Univ-ersitat, Schillingalle 70, 18055 Rostock, Germany tt Author to whom correspondence should be addressed. Abbreviations: Ig, immunoglobulin; TCR, T cell receptor; KW, Kabat-Wu diversity; JAM, Jores-Alzari-Meo diversity; GRASP, Graphical Representation and Analysis of Surface Properties; CDR, complementary-determining region; APC, antigen-presenting cell.
PY - 1997/10
Y1 - 1997/10
N2 - In 1970, before any antigen-bound immunoglobulin structure had been solved, Elvin Kabat proposed that regions of high amino acid diversity would be the antigen binding sites of immunoglobulin. Conversely, sites of low variability were proposed to be structural, framework regions. This variability was defined by Wu and Kabat as the number of different amino acids found at a site divided by the relative frequency of the most common amino acid at that site. Several groups have subsequently devised improvements of Kabat-Wu variability analysis. While these methods are somewhat better than Kabat-Wu, they still suffer from Kabat-Wu's basic limitation: they account for only the most common one or two amino acids in estimating diversity. This leads to underestimates of low diversities and exaggerations of high diversities. Shannon information analysis eliminates serious bias and is more stable than Kabat-Wu and second generation measures of diversity. Statistical reliability can be measured using Shannon analysis, and Shannon measurements can be provided with error estimates. Here we use Shannon's method to analyze the amino acid diversity at each site of T cell receptor V(α) and V(β) to identify complementarity determining regions and framework sites. Our results reveal that the T cell receptor is significantly more diverse than immunoglobulin-suggesting T cell receptor has more than the previously-discovered four complementarity determining regions. These new complementarity determining regions may represent a larger antigen combining site, additional combining sites, or an evolutionary strategy to avoid inappropriate interaction with other molecules.
AB - In 1970, before any antigen-bound immunoglobulin structure had been solved, Elvin Kabat proposed that regions of high amino acid diversity would be the antigen binding sites of immunoglobulin. Conversely, sites of low variability were proposed to be structural, framework regions. This variability was defined by Wu and Kabat as the number of different amino acids found at a site divided by the relative frequency of the most common amino acid at that site. Several groups have subsequently devised improvements of Kabat-Wu variability analysis. While these methods are somewhat better than Kabat-Wu, they still suffer from Kabat-Wu's basic limitation: they account for only the most common one or two amino acids in estimating diversity. This leads to underestimates of low diversities and exaggerations of high diversities. Shannon information analysis eliminates serious bias and is more stable than Kabat-Wu and second generation measures of diversity. Statistical reliability can be measured using Shannon analysis, and Shannon measurements can be provided with error estimates. Here we use Shannon's method to analyze the amino acid diversity at each site of T cell receptor V(α) and V(β) to identify complementarity determining regions and framework sites. Our results reveal that the T cell receptor is significantly more diverse than immunoglobulin-suggesting T cell receptor has more than the previously-discovered four complementarity determining regions. These new complementarity determining regions may represent a larger antigen combining site, additional combining sites, or an evolutionary strategy to avoid inappropriate interaction with other molecules.
UR - http://www.scopus.com/inward/record.url?scp=0031427052&partnerID=8YFLogxK
U2 - 10.1016/S0161-5890(97)00130-2
DO - 10.1016/S0161-5890(97)00130-2
M3 - Journal articles
C2 - 9519765
AN - SCOPUS:0031427052
SN - 0161-5890
VL - 34
SP - 1067
EP - 1082
JO - Molecular Immunology
JF - Molecular Immunology
IS - 15
ER -