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Marc H.V. Van Regenmortel

Marc H.V. Van Regenmortel

University of Strasbourg, France

Title: Specificity, polyspecificity and heterospecificity of virus-antibody interactions

Biography

Marc H V Van Regenmortel is currently an Emeritus Research Director at the CNRS (French National Research Center) in the School of Biotechnology of the University of Strasbourg, France. He was for 22 years Director of the Immunochemistry Laboratory at the CNRS Molecular Biology Institute in Strasbourg and previously was a professor at several universities in South Africa and France. He served (1984-1990) as Vice Chairman and Chairman of the Virology Division of the International Union of Microbiological Societies (IUMS) and was Secretary General of IUMS from 1990 to 1999. He was also for six years (1996-2002) President of the International Committee on Taxonomy of Viruses. He supervised the research work of 30 PhD students and has published 395 research and review papers as well as 17 books in the fields of Virology and Immunochemistry. In 2009 he co-edited with Brian Mahy of the CDC in Atlanta, the third edition of the Encyclopedia of Virology in 5 volumes published by Elsevier. He is currently Editor-in-Chief of Archives of Virology and Journal of Molecular Recognition, An Executive Editor of Analytical Biochemistry, An Associate Editor of Advances in Virus Research, Frontiers in Immunotherapies and Vaccines, Journal of Immunological Methods, ISRN Immunology, Bionomina and Expert Reviews of Proteomics

Abstract

The term specificity is derived from the word species. In the 19th century bacteriologists believed that antisera\\r\\nraised against different species of bacteria were completely specific, allowing different species to be identified\\r\\nwith absolute certainly.\\r\\nAntibody specificity arises in the potential binding site of Igs that consist of 6 CDR loops. The 50-70 hypervariable\\r\\nCDR residues are able to recognize hundreds of epitopes through hundreds of overlapping paratopes of ± 15\\r\\nresidues. Antibodies are usually given names suggesting that they are specific for a particular antigen or protein\\r\\nharboring numerous epitopes. However, an Ab is never specific for a multi-epitopic protein but only for one of its\\r\\nepitopes.\\r\\nA pattern of hydropathic complementarity usually exists between peptides that bind to each other. Complementary\\r\\nstrands of ds DNA or RNA are called “sense” and “antisense”. The anti-sense DNA strand is used as template\\r\\nto produce the mRNA sense transcript which is translated into protein. There is no exception to the rule that\\r\\nDNA/RNA codons (sense) and anti-codons (anti-sense) always code for AA of opposite hydropathicity (i.e.\\r\\neither hydrophilic or hydrophobic residues). As a result peptides coded by two complementary RNA strands\\r\\ntend to bind to each other (2). The specificity of these interactions is due to amino acids collectively forming\\r\\ncomplementary protrusions and cavities, as well as charge and hydropathy fields which fit each other. Peptides of\\r\\nopposite hydropathy bind to each other because hydrophilic residues are oriented towards the aqueous solvent,\\r\\nliberating a space which can accommodate a hydrophobic residue from the opposite chain.\\r\\nEach polyspecific Ab in a polyclonal antiserum cross-reacts with many epitopes that are different for each Ab.\\r\\nSince the collective cross-reactive potential of an antiserum is diluted out, the cross-reactivities of the different\\r\\nantibodies are not apparent. Specific interactions between viruses and antisera arise from the combined effect of\\r\\nseveral independent recognition events. Immunological specificity is not due to a unique and rare Ab that binds\\r\\nonly one particular epitope in an antigen, but arises from the combinatorial effect of different Abs in an antiserum\\r\\nthat recognize separate epitopes on the same antigen.\\r\\nAlthough a paratope tends to react with higher affinity with the homologous epitope used to raise the antibody\\r\\nthan with cross-reacting epitopes, it may also bind more strongly to other epitopes because of heterospecificity.\\r\\nHeterospecificity which is more easily detected with Mabs, is extremely common but is seldom noticed because it\\r\\nis not being looked for (for instance by testing the Ab with Ag analogs). Heterospecificity is due to the fact that the\\r\\nclonal selection of a B cell which eventually leads to affinity maturation and antibody secretion, can be triggered by\\r\\nan immunogen endowed with only moderate affinity for a B cell receptor. Antibody polyspecificity then allows the\\r\\nlow affinity antibodies to react better with related epitopes endowed with a superior degree of complementarity\\r\\nwith the paratope.