Evolving concepts of specificity in immune reactions
- 20 December 2010
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (52), 22373-22380
- https://doi.org/10.1073/pnas.1012051108
Abstract
Our goal is to provide a perspective on current understanding of the origins of specificity in immune reactions, a topic that has intrigued scientists for over a century. A fundamental property of adaptive immune responses is the ability to discriminate among an immense variety of substances by means of antibodies (Abs) and Ab-like receptors on T lymphocytes [T-cell receptors (TCRs)], each able to bind a particular chemical structure [the antigen (Ag)] and not, or only weakly, similar alternatives. Evidence has long existed, however, and has grown, especially recently, that while exhibiting remarkable specificity, many individual Abs and TCRs can also bind a variety of very different ligands. How can Ag recognition by these receptors exercise the great specificity for which they are renowned and yet react with a variety of different ligands (degeneracy)? We critically consider the mechanistic bases for this specificity/degeneracy enigma and also compare and contrast Ag recognition by Abs and TCRs.Keywords
This publication has 115 references indexed in Scilit:
- Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infectionNature, 2010
- T Cell Receptor Cross-reactivity Directed by Antigen-Dependent Tuning of Peptide-MHC Molecular FlexibilityImmunity, 2009
- Digital Signaling and Hysteresis Characterize Ras Activation in Lymphoid CellsCell, 2009
- Conformational changes and flexibility in T-cell receptor recognition of peptide–MHC complexesBiochemical Journal, 2008
- Crossreactive T Cells Spotlight the Germline Rules for αβ T Cell-Receptor Interactions with MHC MoleculesImmunity, 2008
- AID-Dependent Activation of a MYC Transgene Induces Multiple Myeloma in a Conditional Mouse Model of Post-Germinal Center MalignanciesCancer Cell, 2008
- Kinetic evidence for a ligand-binding-induced conformational transition in the T cell receptorProceedings of the National Academy of Sciences of the United States of America, 2007
- Autoreactivity in Human IgG+ Memory B CellsImmunity, 2007
- Antibody evolution constrains conformational heterogeneity by tailoring protein dynamicsProceedings of the National Academy of Sciences, 2006
- Variability in the Lambda Light Chain Sequences of Mouse AntibodyNature, 1970