complementarity determining regions

Summary

Summary: Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL).

Top Publications

  1. Fujino Y, Fujita R, Wada K, Fujishige K, Kanamori T, Hunt L, et al. Robust in vitro affinity maturation strategy based on interface-focused high-throughput mutational scanning. Biochem Biophys Res Commun. 2012;428:395-400 pubmed publisher
    ..45 pM with only 7 amino acid substitutions. The method should facilitate affinity engineering of a wide variety of protein-protein interactions due to its context-dependent library design strategy. ..
  2. Matulis G, Sanderson J, Lissin N, Asparuhova M, Bommineni G, Schumperli D, et al. Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop. PLoS Biol. 2010;8:e1000402 pubmed publisher
    ..This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells. ..
  3. Tschumper R, Asmann Y, Hossain A, Huddleston P, Wu X, Dispenzieri A, et al. Comprehensive assessment of potential multiple myeloma immunoglobulin heavy chain V-D-J intraclonal variation using massively parallel pyrosequencing. Oncotarget. 2012;3:502-13 pubmed
    ..This study demonstrates the power and potential weaknesses of in-depth sequencing as a tool to thoroughly investigate the phylogeny of malignant PCs in MM and the IGHV repertoire of normal BMPCs. ..
  4. Naumova E, Gorski J, Naumov Y. Two compensatory pathways maintain long-term stability and diversity in CD8 T cell memory repertoires. J Immunol. 2009;183:2851-8 pubmed publisher
    ..The recruitment of new clonotypes into the low-frequency component of the repertoire implies a role for these clonotypes. ..
  5. Strokappe N, Szynol A, Aasa Chapman M, Gorlani A, Forsman Quigley A, Hulsik D, et al. Llama antibody fragments recognizing various epitopes of the CD4bs neutralize a broad range of HIV-1 subtypes A, B and C. PLoS ONE. 2012;7:e33298 pubmed publisher
    ..A9 (subtype A) and 96ZM651.02 (subtype C). These findings and the well-known stability of VHH indicate the potential application of these VHH as anti-HIV-1 microbicides. ..
  6. Chen W, Zhu Z, Feng Y, Dimitrov D. A large human domain antibody library combining heavy and light chain CDR3 diversity. Mol Immunol. 2010;47:912-21 pubmed publisher
    ..5 x 10(10)) dAb library by grafting human antibody heavy chain complementarity determining regions (CDRs) 2 and 3 (H2s, H3s) into their cognate positions in a human heavy chain variable domain (VH) ..
  7. Alam S, Liao H, Dennison S, Jaeger F, Parks R, Anasti K, et al. Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation. J Virol. 2011;85:11725-31 pubmed publisher
    ..Thus, these data demonstrate a genetically determined trait that may affect host responses to HIV-1 envelope epitopes recognized by broadly neutralizing antibodies and has implications for unmutated ancestor-based immunogen design. ..
  8. Arnaout R, Lee W, Cahill P, Honan T, Sparrow T, Weiand M, et al. High-resolution description of antibody heavy-chain repertoires in humans. PLoS ONE. 2011;6:e22365 pubmed publisher
    ..Finally, we find that while there are a near-infinite number of heavy-chain CDR3s in principle, there are about 3-9 million in the blood of an adult human being. ..
  9. Perchiacca J, Bhattacharya M, Tessier P. Mutational analysis of domain antibodies reveals aggregation hotspots within and near the complementarity determining regions. Proteins. 2011;79:2637-47 pubmed publisher
    ..for human V(H) domain antibodies that differ only in the sequence of the loops containing their complementarity determining regions (CDRs), yet such antibodies possess dramatically different aggregation propensities in a manner not ..

More Information

Publications62

  1. Murakami A, Takahashi Y, Nishimura M, Shimizu T, Azuma T. The amino acid residue at position 95 and the third CDR region in the H chain determine the ceiling affinity and the maturation pathway of an anti-(4-hydroxy-3-nitrophenyl)acetyl antibody. Mol Immunol. 2010;48:48-58 pubmed publisher
  2. Vale A, Tanner J, Schelonka R, Zhuang Y, Zemlin M, Gartland G, et al. The peritoneal cavity B-2 antibody repertoire appears to reflect many of the same selective pressures that shape the B-1a and B-1b repertoires. J Immunol. 2010;185:6085-95 pubmed publisher
    ..The PerC may thus serve as a general reservoir for B cells with Ag binding specificities that are uncommon in other mature compartments...
  3. Koti M, Kataeva G, Kaushik A. Novel atypical nucleotide insertions specifically at VH-DH junction generate exceptionally long CDR3H in cattle antibodies. Mol Immunol. 2010;47:2119-28 pubmed publisher
  4. Scott Browne J, White J, Kappler J, Gapin L, Marrack P. Germline-encoded amino acids in the alphabeta T-cell receptor control thymic selection. Nature. 2009;458:1043-6 pubmed publisher
  5. Schroeder H, Zemlin M, Khass M, Nguyen H, Schelonka R. Genetic control of DH reading frame and its effect on B-cell development and antigen-specifc antibody production. Crit Rev Immunol. 2010;30:327-44 pubmed
    ..This change in the repertoire variably affects antibody production and the development of specific B-cell subsets. ..
  6. Pantazes R, Maranas C. OptCDR: a general computational method for the design of antibody complementarity determining regions for targeted epitope binding. Protein Eng Des Sel. 2010;23:849-58 pubmed publisher
    ..First, combinations of canonical structures for the antibody complementarity determining regions (CDRs) that are most likely to be able to favorably bind the antigen are selected...
  7. Zhang J, Yip H, Katta V. Identification of isomerization and racemization of aspartate in the Asp-Asp motifs of a therapeutic protein. Anal Biochem. 2011;410:234-43 pubmed publisher
    ..Another isomerization site was identified as Asp-24 in the heavy chain peptide H5 QAPGQGLEWMGWINTYTGETTYAD(24)DFK. No other isomerizations were detected in CDR peptides containing either Asp-Ser or Asp-Thr motifs. ..
  8. Scott D, Borbulevych O, Piepenbrink K, CORCELLI S, Baker B. Disparate degrees of hypervariable loop flexibility control T-cell receptor cross-reactivity, specificity, and binding mechanism. J Mol Biol. 2011;414:385-400 pubmed publisher
  9. Lingwood D, McTamney P, Yassine H, Whittle J, Guo X, Boyington J, et al. Structural and genetic basis for development of broadly neutralizing influenza antibodies. Nature. 2012;489:566-70 pubmed publisher
    ..The data further suggest that selected immunoglobulin genes recognize specific protein structural 'patterns' that provide a substrate for further affinity maturation. ..
  10. Singh V, Stoop M, Stingl C, Luitwieler R, Dekker L, van Duijn M, et al. Cerebrospinal-fluid-derived immunoglobulin G of different multiple sclerosis patients shares mutated sequences in complementarity determining regions. Mol Cell Proteomics. 2013;12:3924-34 pubmed publisher
    ..Recent studies indicate that the complementarity determining regions of immunoglobulins specific for certain antigens are frequently shared between different ..
  11. de Costa D, Broodman I, VanDuijn M, Stingl C, Dekker L, Burgers P, et al. Sequencing and quantifying IgG fragments and antigen-binding regions by mass spectrometry. J Proteome Res. 2010;9:2937-45 pubmed publisher
    ..From these results, we conclude that the identification of a CDR signature as biomarker for autoimmune diseases and cancer without prior knowledge of the antigen is feasible. ..
  12. Yan B, Steen S, Hambly D, Valliere Douglass J, Vanden Bos T, Smallwood S, et al. Succinimide formation at Asn 55 in the complementarity determining region of a recombinant monoclonal antibody IgG1 heavy chain. J Pharm Sci. 2009;98:3509-21 pubmed publisher
    ..Hydrolysis of the succinimide resulted in a further drop in potency. The implications of the succinimide formation at Asn 55, a highly conserved residue among IgG1 (mAbs), are discussed. ..
  13. Xi X, Guo Y, Chen H, Xu C, Zhang H, Hu H, et al. Antigen specificity of gammadelta T cells depends primarily on the flanking sequences of CDR3delta. J Biol Chem. 2009;284:27449-55 pubmed publisher
    ..Our results demonstrate that TCRdelta primarily uses conserved flanking regions to bind ligands. This finding may provide an explanation for the limited number of gammadelta TCR ligands that have as yet been identified. ..
  14. Montgomery D, Wang Y, Hrin R, Luftig M, Su B, Miller M, et al. Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41. MAbs. 2009;1:462-74 pubmed
    ..Both binding and neutralization depend on residues in the complementarity determining regions (CDRs) of the D5 IgG variable domains on heavy chain (VH) and light chain (VL)...
  15. Hinz A, Lutje Hulsik D, Forsman A, Koh W, Belrhali H, Gorlani A, et al. Crystal structure of the neutralizing Llama V(HH) D7 and its mode of HIV-1 gp120 interaction. PLoS ONE. 2010;5:e10482 pubmed publisher
    ..5 A resolution, which reveals the molecular details of the complementarity determining regions (CDR) and substantial flexibility of CDR3 that could facilitate an induced fit interaction with ..
  16. Zabetakis D, Anderson G, Bayya N, Goldman E. Contributions of the complementarity determining regions to the thermal stability of a single-domain antibody. PLoS ONE. 2013;8:e77678 pubmed publisher
    ..The goal of this work was to determine how much of sdAb A3's stability is derived from its complementarity determining regions (CDRs) versus its framework...
  17. Piepenbrink K, Blevins S, Scott D, Baker B. The basis for limited specificity and MHC restriction in a T cell receptor interface. Nat Commun. 2013;4:1948 pubmed publisher
  18. McConnell A, Spasojevich V, Macomber J, Krapf I, Chen A, Sheffer J, et al. An integrated approach to extreme thermostabilization and affinity maturation of an antibody. Protein Eng Des Sel. 2013;26:151-64 pubmed publisher
  19. Kunik V, Peters B, Ofran Y. Structural consensus among antibodies defines the antigen binding site. PLoS Comput Biol. 2012;8:e1002388 pubmed publisher
    The Complementarity Determining Regions (CDRs) of antibodies are assumed to account for the antigen recognition and binding and thus to contain also the antigen binding site...
  20. Wu L, Oficjalska K, Lambert M, Fennell B, Darmanin Sheehan A, Ní Shúilleabháin D, et al. Fundamental characteristics of the immunoglobulin VH repertoire of chickens in comparison with those of humans, mice, and camelids. J Immunol. 2012;188:322-33 pubmed publisher
    ..This study supports the hypothesis that disulfide bond-constrained CDR3s are a structural diversification strategy in the restricted germline v-gene repertoire of chickens. ..
  21. Forconi F, Potter K, Wheatley I, Darzentas N, Sozzi E, Stamatopoulos K, et al. The normal IGHV1-69-derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL. Blood. 2010;115:71-7 pubmed publisher
    ..Conserved patterns in the 51p1-encoded immunoglobulin M of normal B cells suggest a restricted sequence repertoire shaped by evolution to recognize common pathogens. Proliferative pressure on these cells is the likely route to U-CLL. ..
  22. Ofek G, McKee K, Yang Y, Yang Z, Skinner J, Guenaga F, et al. Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region. J Virol. 2010;84:2955-62 pubmed publisher
    ..Together, the results provide a more complete understanding of the 2F5 mechanism of HIV-1 neutralization and indicate ways to enhance the potency of MPER-directed antibodies. ..
  23. Xi X, Cui L, He W. The recognition of gammadelta TCR to protein antigen does not depend on the hydrophobic I97 residue of CDR3delta. Int Immunol. 2010;22:299-306 pubmed publisher
    ..This finding may provide a possibility that gammadelta TCR recognize different ligands in diversity manners. ..
  24. Ravn U, Gueneau F, Baerlocher L, Osteras M, Desmurs M, Malinge P, et al. By-passing in vitro screening--next generation sequencing technologies applied to antibody display and in silico candidate selection. Nucleic Acids Res. 2010;38:e193 pubmed publisher
  25. Gold M, Cerri S, Smyk Pearson S, Cansler M, Vogt T, Delepine J, et al. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol. 2010;8:e1000407 pubmed publisher
    ..Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection. ..
  26. Reddy S, Ge X, Miklos A, Hughes R, Kang S, Hoi K, et al. Monoclonal antibodies isolated without screening by analyzing the variable-gene repertoire of plasma cells. Nat Biotechnol. 2010;28:965-9 pubmed publisher
    ..Antibodies generated in this manner from six mice, each immunized with one of three antigens were overwhelmingly antigen specific (21/27 or 78%). Those generated from a mouse with high serum titers had nanomolar binding affinities...
  27. Timmerman P, Shochat S, Desmet J, Barderas R, Casal J, Meloen R, et al. Binding of CDR-derived peptides is mechanistically different from that of high-affinity parental antibodies. J Mol Recognit. 2010;23:559-68 pubmed publisher
    ..We speculate that our findings are of general relevance, in showing that high-affinity mAbs do not necessarily provide the optimal basis for functional mimics design. ..
  28. Parameswaran P, Liu Y, Roskin K, Jackson K, Dixit V, Lee J, et al. Convergent antibody signatures in human dengue. Cell Host Microbe. 2013;13:691-700 pubmed publisher
    ..Dengue thus provides a striking example of a human viral infection where convergent immune signatures can be identified in multiple individuals. Such signatures could facilitate surveillance of immunological memory in communities. ..
  29. Wang Q, Hanada K, Feldman S, Zhao Y, Inozume T, Yang J. Development of a genetically-modified novel T-cell receptor for adoptive cell transfer against renal cell carcinoma. J Immunol Methods. 2011;366:43-51 pubmed publisher
    ..A phase I/II clinical trial, adoptively transferring autologous PBL transduced with this modified TCR has just begun in patients with metastatic RCC. ..
  30. Xu B, Pizarro J, Holmes M, McBeth C, Groh V, Spies T, et al. Crystal structure of a gammadelta T-cell receptor specific for the human MHC class I homolog MICA. Proc Natl Acad Sci U S A. 2011;108:2414-9 pubmed publisher
    ..Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of ?? T-cell/target cell interfaces. ..
  31. Wine Y, Boutz D, Lavinder J, Miklos A, Hughes R, Hoi K, et al. Molecular deconvolution of the monoclonal antibodies that comprise the polyclonal serum response. Proc Natl Acad Sci U S A. 2013;110:2993-8 pubmed publisher
    ..Antibody V-gene sequences are characterized by short complementarity determining regions (CDRs) of high diversity adjacent to framework regions shared across thousands of IgGs, greatly ..
  32. Kumagai K, Hamada Y, Gotoh A, Kobayashi H, Kawaguchi K, Horie A, et al. Evidence for the changes of antitumor immune response during lymph node metastasis in head and neck squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110:341-50 pubmed publisher
    ..These results suggest that lymph node metastasis might be associated with changes in the nature of the primary tumor antigens. ..
  33. Birtalan S, Fisher R, Sidhu S. The functional capacity of the natural amino acids for molecular recognition. Mol Biosyst. 2010;6:1186-94 pubmed publisher
    ..Moreover, our findings illuminate the fundamental principles underlying protein-protein interactions and provide valuable guidelines for engineering synthetic binding proteins with functions beyond the scope of natural proteins. ..
  34. Harding F, Stickler M, Razo J, DuBridge R. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs. 2010;2:256-65 pubmed
    ..Modifications to CDR regions can be designed that reduce the immunogenic potential while maintaining the bioactivity of the antibody molecule. ..
  35. Krawczyk K, Baker T, Shi J, Deane C. Antibody i-Patch prediction of the antibody binding site improves rigid local antibody-antigen docking. Protein Eng Des Sel. 2013;26:621-9 pubmed publisher
    ..Our annotation method and re-scoring system for docking achieve their predictive power by using antibody-specific statistics. Antibody i-Patch is available from http://www.stats.ox.ac.uk/research/proteins/resources. ..
  36. Bostrom J, Yu S, Kan D, Appleton B, Lee C, Billeci K, et al. Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science. 2009;323:1610-4 pubmed publisher
    ..Such "two-in-one" antibodies challenge the monoclonal antibody paradigm of one binding site, one antigen. They could also provide new opportunities for antibody-based therapy. ..
  37. Holland S, Bartok I, Attaf M, Genolet R, Luescher I, Kotsiou E, et al. The T-cell receptor is not hardwired to engage MHC ligands. Proc Natl Acad Sci U S A. 2012;109:E3111-8 pubmed publisher
    ..To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo...
  38. Weinstein J, Jiang N, White R, Fisher D, Quake S. High-throughput sequencing of the zebrafish antibody repertoire. Science. 2009;324:807-10 pubmed publisher
    ..This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism. ..
  39. Petrovskaya L, Shingarova L, Kryukova E, Boldyreva E, Yakimov S, Guryanova S, et al. Construction of TNF-binding proteins by grafting hypervariable regions of F10 antibody on human fibronectin domain scaffold. Biochemistry (Mosc). 2012;77:62-70 pubmed publisher
    ..The highest neutralizing activity was demonstrated by the proteins Hd2 and Hd3, which induced, respectively, 10- and 50-fold increase in the EC(50) of TNF. ..
  40. Robins H, Srivastava S, Campregher P, Turtle C, Andriesen J, Riddell S, et al. Overlap and effective size of the human CD8+ T cell receptor repertoire. Sci Transl Med. 2010;2:47ra64 pubmed publisher
    ..Surprisingly, the overlap in the naïve CD8(+) CDR3 sequence repertoires of any two of the individuals is approximately 7000-fold larger than predicted and appears to be independent of the degree of human leukocyte antigen matching. ..
  41. Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, Wang C, et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science. 2011;333:1593-602 pubmed publisher
  42. Dekker L, Zeneyedpour L, Brouwer E, van Duijn M, Sillevis Smitt P, Luider T. An antibody-based biomarker discovery method by mass spectrometry sequencing of complementarity determining regions. Anal Bioanal Chem. 2011;399:1081-91 pubmed publisher
    ..As an alternative approach, we propose to identify specific complementarity determining regions (CDR) of IgG that relate to an autoimmune disorder or cancer instead of the specific antigen(s)...
  43. Guo W, Smith D, Aviszus K, Detanico T, Heiser R, Wysocki L. Somatic hypermutation as a generator of antinuclear antibodies in a murine model of systemic autoimmunity. J Exp Med. 2010;207:2225-37 pubmed publisher
    ..Our findings reveal the predominant role of SHM in the development of ANA and underscore the importance of self-tolerance checkpoints at the postmutational stage of B cell differentiation. ..
  44. Robins H, Campregher P, Srivastava S, Wacher A, Turtle C, Kahsai O, et al. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood. 2009;114:4099-107 pubmed publisher
    ..These methods should prove valuable for assessment of alphabeta T-cell repertoire diversity after hematopoietic cell transplantation, in states of congenital or acquired immunodeficiency, and during normal aging. ..
  45. Choi Y, Deane C. Predicting antibody complementarity determining region structures without classification. Mol Biosyst. 2011;7:3327-34 pubmed publisher
    Antibodies are used extensively in medical and biological research. Their complementarity determining regions (CDRs) define the majority of their antigen binding functionality...
  46. Larsen P, Smith T. Application of circular consensus sequencing and network analysis to characterize the bovine IgG repertoire. BMC Immunol. 2012;13:52 pubmed publisher
    ..We hypothesize that network or cluster-based analyses of expressed antibody repertoires from controlled challenge experiments will help identify novel natural antigen binding solutions to specific pathogens of interest. ..
  47. Zhao S, Lu J. A germline knowledge based computational approach for determining antibody complementarity determining regions. Mol Immunol. 2010;47:694-700 pubmed publisher
    Determination of framework regions (FRs) and complementarity determining regions (CDRs) in an antibody is essential for understanding the underlying biology as well as antibody engineering and optimization...
  48. Mwangi W, Beal R, Powers C, Wu X, Humphrey T, Watson M, et al. Regional and global changes in TCRalphabeta T cell repertoires in the gut are dependent upon the complexity of the enteric microflora. Dev Comp Immunol. 2010;34:406-17 pubmed publisher
    ..These data indicate the dramatic influence of enteric microflora complexity on the profile of TCRbeta repertoire in the gut at local and global levels. ..
  49. Kalinina O, Doyle Cooper C, Miksanek J, Meng W, Prak E, Weigert M. Alternative mechanisms of receptor editing in autoreactive B cells. Proc Natl Acad Sci U S A. 2011;108:7125-30 pubmed publisher
    ..The editing mechanisms in the case of ?-expressing B cells include L chain allelic inclusion and V(H) replacement. ..
  50. Pancera M, McLellan J, Wu X, Zhu J, Changela A, Schmidt S, et al. Crystal structure of PG16 and chimeric dissection with somatically related PG9: structure-function analysis of two quaternary-specific antibodies that effectively neutralize HIV-1. J Virol. 2010;84:8098-110 pubmed publisher
    ..The structural and functional details of extraordinary CDR H3 and extensive affinity maturation provide insights into the neutralization mechanism of and the elicitation pathway for broadly neutralizing antibodies like PG9 and PG16. ..
  51. Julien J, Huarte N, Maeso R, Taneva S, Cunningham A, Nieva J, et al. Ablation of the complementarity-determining region H3 apex of the anti-HIV-1 broadly neutralizing antibody 2F5 abrogates neutralizing capacity without affecting core epitope binding. J Virol. 2010;84:4136-47 pubmed publisher
    ..The present data therefore imply an extended 2F5 paratope that includes weak secondary interactions that are crucial for neutralization of Env-mediated fusion. ..
  52. North B, Lehmann A, Dunbrack R. A new clustering of antibody CDR loop conformations. J Mol Biol. 2011;406:228-56 pubmed publisher
    ..Thus, the earlier analyses have been significantly enhanced by the increased data. We believe that the new classification will lead to improved methods for antibody structure prediction and design. ..
  53. Prabakaran P, Gan J, Wu Y, Zhang M, Dimitrov D, Ji X. Structural mimicry of CD4 by a cross-reactive HIV-1 neutralizing antibody with CDR-H2 and H3 containing unique motifs. J Mol Biol. 2006;357:82-99 pubmed
    ..Thus, vaccine immunogens based on the m18 epitope structure are unlikely to elicit antibodies that could enhance infection. The structure can also serve as a basis for the design of novel, highly efficient inhibitors of HIV entry. ..