Analysis of the antigen combining site: correlations between length and sequence composition of the hypervariable loops and the nature of the antigen.
It has long been suggested that the overall shape of the antigen combining site (ACS) of antibodies is correlated with the nature of the antigen. For example, deep pockets are characteristic of antibodies that bind haptens, grooves indicate peptide binders, while antibodies that bind to proteins have relatively flat combining sites. In 1996, MacCallum, Martin and Thornton used a fractal shape descriptor and showed a strong correlation of the shape of the binding region with the general nature of the antigen.However, the shape of the ACS is determined primarily by the lengths of the six complementarity-determining regions (CDRs). Here, we make a direct correlation between the lengths of the CDRs and the nature of the antigen. In addition, we show significant differences in the residue composition of the CDRs of antibodies that bind to different antigen classes. As well as helping us to understand the process of antigen recognition, autoimmune disease and cross-reactivity, these results are of direct application in the design of antibody phage libraries and modification of affinity.
Collis
Abigail V J
AV
School of Animal and Microbial Sciences, University of Reading, Whiteknights, P.O. Box 228, UK.
Brouwer
Adam P
AP
Martin
Andrew C R
AC
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000378:metabolism; D000918:Antibody Specificity; D000941:Antigens / Q000737:chemistry* / Q000378:metabolism; D001666:Binding Sites, Antibody; D016009:Chi-Square Distribution; D022801:Complementarity Determining Regions / Q000737:chemistry* / Q000378:metabolism; D016208:Databases, Factual; D006801:Humans; D051379:Mice; D011487:Protein Conformation; D020539:Sequence Analysis, Protein
D000596:Amino Acids; D000906:Antibodies; D000941:Antigens; D022801:Complementarity Determining Regions