The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

CDR3  -  Cerebellar degeneration-related autoantigen-3

Homo sapiens

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CDR3

  • An antibody that binds the immunoglobulin CDR3-like region of the CD4 molecule inhibits provirus transcription in HIV-infected T cells [1].
  • The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous ("stereotyped") complementarity-determining region 3 (CDR3) sequences [2].
  • CDR3 of the functional rearranged T-cell receptor variable beta region (TCR-Vbeta) transcript was sequenced in order to demonstrate for the first time the identity between a long-term cultured T-cell line derived from a cutaneous T-cell lymphoma (CTCL) patient and the malignant T-cell clone present in the blood [3].
  • Here we investigated the role of p56Ick in the cascade of molecular events that control HIV-1 transcription in cells treated with anti-CD4 mAb directed against the Ig CDR3-like region [4].
  • These results strongly suggest i) that soluble gp120 and virion-anchored gp120 bind CD4 in distinct manners, ii) that gp120-CD4 interactions required for viral entry and syncytia formation are different, and iii) that mAb binding to the CDR3-like region of the first domain of CD4 affects a post-entry step of the HIV replicative cycle [5].

Psychiatry related information on CDR3

  • Our results: (1) extend the concept that CDR3 diversity is essential for Ag and Id specificity to a polysaccharide-binding Ab; (2) show that aa conservation in CDRs does not imply a requirement for Ag binding; (3) establish a role for W36 in secretion; and (4) demonstrate that aa motifs used for binding GXM and peptide mimetics can differ [6].
  • To this end we generated CDR3-specific cDNA libraries from tissues collected at several stages of human development [7].
  • Our results suggest that not only scFvs recognizing Abeta42 but also synthetic peptides based on the V(H) CDR3 sequences of these antibodies may be novel potential candidates for small molecule-based Alzheimer's disease (AD) therapy [8].
  • The hippocampus and entorhinal cortex were examined in 13 nondemented cases (Clinical Dementia Rating [CDR] 0) with healthy brains, 4 cases with preclinical AD, 8 cases with very mild symptomatic AD (CDR 0.5), and 4 cases with severe AD (CDR 3, hippocampus only) [9].

High impact information on CDR3

  • T cells constantly sample their environment using receptors (TCR) that possess both a germline-encoded low affinity for major histocompatibility complex (MHC) molecules and a highly diverse set of CDR3 regions contributing to a range of affinities for specific peptides bound to these MHC molecules [10].
  • We conclude with an analysis of the highly diverse CDR3 loops found in all antigen receptor molecules and suggest that such regions form the core of both TCR and antibody specificity [11].
  • Intraclonal variation in nucleotide sequences suggests that hypermutation of the heavy-chain CDR3 continues to occur among the clonal progeny [12].
  • The heavy-chain CDR3 of each cell was amplified by the polymerase chain reaction [12].
  • METHODS: We used complementarity-determining region 3 (CDR3) of the immunoglobulin heavy-chain gene as a clonal marker to study individual L&H cells isolated by micromanipulation from tissue sections of five patients with nodular lymphocyte-predominant Hodgkin's disease [12].

Chemical compound and disease context of CDR3


Biological context of CDR3

  • Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities [18].
  • Previous analyses of a cDNA library generated from synovium of RA patient BC revealed immunoglobulin kappa light chain transcripts with extensive somatic mutation, frequent N region addition, and unexpected variation in the lengths of CDR3 regions which form the center of the antigen binding site [19].
  • Using Poisson distribution analysis of positive polymerase chain reactions with patient-specific complementarity-determining region 1 (CDR1) and CDR3 Ig-gene primers, tumor was detected in leukapheresis products from 8 to 14 unselected patients and ranged from 1.13 x 10(4) to 2.14 x 10(6) malignant cells/kg [20].
  • We used flow cytometry to outline the exact TCR V gene expression, complementarity determining region 3 (CDR3) fragment analysis to estimate the degree of clonality and cDNA sequencing to define the exact TCR or beta chain sequences [21].
  • Amino acid sequences of these beta-chains suggested hypothetical contact points for Ni2+ ions in complementarity-determining region (CDR) 1 and CDR3 [22].

Anatomical context of CDR3

  • These results are consistent with a model in which the highly diverse CDR3 loops are the key determinant of specificity in antigen recognition in both T cell receptors (TCR) and antibodies, whereas the germline-encoded CDR1 and CDR2 sequences are much more cross-reactive [18].
  • Significant expression of transcripts containing these unique CDR3 sequences occurred only in the patient's synovium [23].
  • After in vitro stimulation of T cells with autologous leukemic B cells, analyses of the CDR3 length patterns showed that in expanded TCR-BV populations, polyclonal patterns frequently shifted toward a monoclonal/oligoclonal profile, whereas largely monoclonal patterns in native overexpressed TCR-BV subsets remained monoclonal [24].
  • Benzylated derivatives of a peptide (CD4(81-92)) representing the CDR3-like region of CD4 were previously found to inhibit gp120 binding, HIV-1 infectivity, and syncytium formation [25].
  • mAbs that bind to the Ig CDR3-like region in D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell lines at the stage of transcription [4].

Associations of CDR3 with chemical compounds

  • Only one important binding site residue Glu-95 of the heavy chain CDR3 is mutated to alanine in the 77 Fab fragment [26].
  • One mutant, M1, at position 97 (Asp to Ala) in CDR3 of the heavy chain, resulted in an 8- to 10-fold improvement in Ag binding, as assessed by ELISA [27].
  • Combining the V(L) of C3 with a human V(H) library, while retaining the V(H) CDR3 of MOC-31, clones were selected using human V(H) genes originating from the rarely used V(H)7 family [28].
  • The salt-sensitive binding was highly correlated with the presence of arginine in the complementarity-determining region 3 (CDR3) [29].
  • Moreover, since additional codons at the recombination site of V kappa and J kappa seem exceptional in expressed human kappa chains and because the resulting amino acid residue is a proline in most cases, we think that RF kappa chain CDR3 is under a very strong selective pressure during RA [30].

Physical interactions of CDR3

  • The cytoplasmic tail of CD4 is required for inhibition of human immunodeficiency virus type 1 replication by antibodies that bind to the immunoglobulin CDR3-like region in domain 1 of CD4 [31].
  • Expression of the FAI (formation of syncytia by shifting from 16 to 37 degrees C) remains sensitive to sCD4, shedding of gp120, and MAb directed toward CDR-1/2 but is less sensitive to MAb that bind CDR-3 and is insensitive to PI [32].
  • The third complementarity-determining region (CDR3) of TCR interacts directly with antigenic peptides bound to grooves of MHC molecules [33].
  • Here we examined the effect of randomizing amino acids in the heavy chain complementarity determining region 3 (CDR3) of this germline encoded recombinant antibody fragment on binding to the U1A protein [34].

Regulatory relationships of CDR3

  • Anti-idiotypic T cells induced by the 8mer TCR peptide were predominantly CD8+ cytotoxic T cells and exhibited cytotoxic activity against autologous MBP-specific T cells expressing the CDR3 sequence [35].
  • Somatic mutation and CDR3 lengths of immunoglobulin kappa light chains expressed in patients with rheumatoid arthritis and in normal individuals [19].
  • Remarkably similar usage of J beta regions was noted, and two individuals demonstrated V beta 3-expressing clones with homologous CDR3 regions, differing by only one major substitution [36].
  • We describe the production and biochemical characterization of the first GPIIb/IIIa-inhibiting monoclonal antibody that contains an RGD sequence in the CDR3 region of the heavy chain [37].
  • The fact that some genes like VH1-69 and VH3-07 recombine this VH segment to particular JH segments and the restricted use of CDR3 sequences by CLLs expressing the VH4-39 gene suggest that the observed differences in BCR structure in B-CLL could result from selection by distinct antigenic epitopes [38].

Other interactions of CDR3

  • Thus, the MYPPPY motifs of CTLA4Ig and CD28Ig are important for their binding to B7-1, but the increased strength of this binding by CTLA4Ig is mediated by nonconserved residues in the CDR1- and CDR3-analogous regions [39].
  • To determine the extent of B lymphocyte involvement, the proportion of clonotypic cells among the CD19-expressing cells from myeloma patients was estimated by quantitative polymerase chain reaction analysis of the third complementarity determining region (CDR3) [40].
  • Our previous mutational analysis of CD28 defined the highly conserved "MYPPPY" motif in the CDR3-region of the V-like domain as a key site of common and selective recognition [41].
  • Characterization of third complementarity determining regions (CDR3) fails to demonstrate a recurring motif characteristic of the T cell immune response to MBP in this species [42].
  • We replaced the nine amino acid CDR3-like loop of CTLA-4 with the sequence XXX-RGD-XXX (where X represents any amino acid) [43].

Analytical, diagnostic and therapeutic context of CDR3


  1. An antibody that binds the immunoglobulin CDR3-like region of the CD4 molecule inhibits provirus transcription in HIV-infected T cells. Benkirane, M., Corbeau, P., Housset, V., Devaux, C. EMBO J. (1993) [Pubmed]
  2. Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations. Stamatopoulos, K., Belessi, C., Moreno, C., Boudjograh, M., Guida, G., Smilevska, T., Belhoul, L., Stella, S., Stavroyianni, N., Crespo, M., Hadzidimitriou, A., Sutton, L., Bosch, F., Laoutaris, N., Anagnostopoulos, A., Montserrat, E., Fassas, A., Dighiero, G., Caligaris-Cappio, F., Merle-B??ral, H., Ghia, P., Davi, F. Blood (2007) [Pubmed]
  3. Functional characterization of an IL-7-dependent CD4(+)CD8alphaalpha(+) Th3-type malignant cell line derived from a patient with a cutaneous T-cell lymphoma. Poszepczynska, E., Bagot, M., Echchakir, H., Martinvalet, D., Ramez, M., Charue, D., Boumsell, L., Bensussan, A. Blood (2000) [Pubmed]
  4. An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not HTLV-I, in a CD4-positive/p56lck-negative HTLV-I-transformed cell line. Lemasson, I., Briant, L., Hague, B., Coudronnière, N., Heron, L., David, C., Rebouissou, C., Kindt, T., Devaux, C. J. Immunol. (1996) [Pubmed]
  5. Ig CDR3-like region of the CD4 molecule is involved in HIV-induced syncytia formation but not in viral entry. Corbeau, P., Benkirane, M., Weil, R., David, C., Emiliani, S., Olive, D., Mawas, C., Serre, A., Devaux, C. J. Immunol. (1993) [Pubmed]
  6. The function of conserved amino acids in or near the complementarity determining regions for related antibodies to Cryptococcus neoformans glucuronoxylomannan. Nakouzi, A., Casadevall, A. Mol. Immunol. (2003) [Pubmed]
  7. Multiple mechanisms participate in the generation of diversity of human H chain CDR3 regions. Sanz, I. J. Immunol. (1991) [Pubmed]
  8. Human single chain Fv antibodies and a complementarity determining region-derived peptide binding to amyloid-beta 1-42. Manoutcharian, K., Acero, G., Munguia, M.E., Becerril, B., Massieu, L., Govezensky, T., Ortiz, E., Marks, J.D., Cao, C., Ugen, K., Gevorkian, G. Neurobiol. Dis. (2004) [Pubmed]
  9. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Price, J.L., Ko, A.I., Wade, M.J., Tsou, S.K., McKeel, D.W., Morris, J.C. Arch. Neurol. (2001) [Pubmed]
  10. The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation. Germain, R.N., Stefanová, I. Annu. Rev. Immunol. (1999) [Pubmed]
  11. Ligand recognition by alpha beta T cell receptors. Davis, M.M., Boniface, J.J., Reich, Z., Lyons, D., Hampl, J., Arden, B., Chien, Y. Annu. Rev. Immunol. (1998) [Pubmed]
  12. Clonality in nodular lymphocyte-predominant Hodgkin's disease. Ohno, T., Stribley, J.A., Wu, G., Hinrichs, S.H., Weisenburger, D.D., Chan, W.C. N. Engl. J. Med. (1997) [Pubmed]
  13. CD4 molecules with a diversity of mutations encompassing the CDR3 region efficiently support human immunodeficiency virus type 1 envelope glycoprotein-mediated cell fusion. Broder, C.C., Berger, E.A. J. Virol. (1993) [Pubmed]
  14. Phage display-selected sequences of the heavy-chain CDR3 loop of the anti-digoxin antibody 26-10 define a high affinity binding site for position 16-substituted analogs of digoxin. Krykbaev, R.A., Liu, W.R., Jeffrey, P.D., Margolies, M.N. J. Biol. Chem. (2001) [Pubmed]
  15. Highly conserved TCR beta chain CDR3 sequences among immunodominant acetylcholine receptor-reactive T cells in murine myasthenia gravis. Pierce, J.L., Zborowski, K.A., Kraig, E., Infante, A.J. Int. Immunol. (1994) [Pubmed]
  16. Individual Vgamma2-Jgamma1.2+ T cells respond to both isopentenyl pyrophosphate and Daudi cell stimulation: generating tumor effectors with low molecular weight phosphoantigens. Hebbeler, A.M., Cairo, C., Cummings, J.S., Pauza, C.D. Cancer Immunol. Immunother. (2007) [Pubmed]
  17. Analysis of T cell receptor beta chain CDR3 size using RNA extracted from formalin fixed paraffin wax embedded tissue. O'Shea, U., Wyatt, J.I., Howdle, P.D. J. Clin. Pathol. (1997) [Pubmed]
  18. Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities. Xu, J.L., Davis, M.M. Immunity (2000) [Pubmed]
  19. Somatic mutation and CDR3 lengths of immunoglobulin kappa light chains expressed in patients with rheumatoid arthritis and in normal individuals. Bridges, S.L., Lee, S.K., Johnson, M.L., Lavelle, J.C., Fowler, P.G., Koopman, W.J., Schroeder, H.W. J. Clin. Invest. (1995) [Pubmed]
  20. Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma. Schiller, G., Vescio, R., Freytes, C., Spitzer, G., Sahebi, F., Lee, M., Wu, C.H., Cao, J., Lee, J.C., Hong, C.H. Blood (1995) [Pubmed]
  21. T-cell expansions with conserved T-cell receptor beta chain motifs in the peripheral blood of HLA-DRB1*0401 positive patients with necrotizing vasculitis. Grunewald, J., Halapi, E., Wahlström, J., Giscombe, R., Nityanand, S., Sanjeevi, C., Lefvert, A.K. Blood (1998) [Pubmed]
  22. TCR reactivity in human nickel allergy indicates contacts with complementarity-determining region 3 but excludes superantigen-like recognition. Vollmer, J., Weltzien, H.U., Moulon, C. J. Immunol. (1999) [Pubmed]
  23. Evidence of antigen receptor-influenced oligoclonal B lymphocyte expansion in the synovium of a patient with longstanding rheumatoid arthritis. Lee, S.K., Bridges, S.L., Kirkham, P.M., Koopman, W.J., Schroeder, H.W. J. Clin. Invest. (1994) [Pubmed]
  24. Leukemia-associated monoclonal and oligoclonal TCR-BV use in patients with B-cell chronic lymphocytic leukemia. Rezvany, M.R., Jeddi-Tehrani, M., Wigzell, H., Osterborg, A., Mellstedt, H. Blood (2003) [Pubmed]
  25. Effects of CD4 synthetic peptides on HIV type I envelope glycoprotein function. Repke, H., Gabuzda, D., Palù, G., Emmrich, F., Sodroski, J. J. Immunol. (1992) [Pubmed]
  26. Crystal structure of an in vitro affinity- and specificity-matured anti-testosterone Fab in complex with testosterone. Improved affinity results from small structural changes within the variable domains. Valjakka, J., Hemminki, A., Niemi, S., Söderlund, H., Takkinen, K., Rouvinen, J. J. Biol. Chem. (2002) [Pubmed]
  27. Affinity maturation of the BR96 anti-carcinoma antibody by codon-based mutagenesis. Yelton, D.E., Rosok, M.J., Cruz, G., Cosand, W.L., Bajorath, J., Hellström, I., Hellström, K.E., Huse, W.D., Glaser, S.M. J. Immunol. (1995) [Pubmed]
  28. Guided selection of a pan carcinoma specific antibody reveals similar binding characteristics yet structural divergence between the original murine antibody and its human equivalent. Beiboer, S.H., Reurs, A., Roovers, R.C., Arends, J.W., Whitelegg, N.R., Rees, A.R., Hoogenboom, H.R. J. Mol. Biol. (2000) [Pubmed]
  29. Comparison of rheumatoid factors of rheumatoid arthritis patients, of individuals with mycobacterial infections and of normal controls: evidence for maturation in the absence of an autoimmune response. Djavad, N., Bas, S., Shi, X., Schwager, J., Jeannet, M., Vischer, T., Roosnek, E. Eur. J. Immunol. (1996) [Pubmed]
  30. Molecular analysis of the V kappa III-J kappa junctional diversity of polyclonal rheumatoid factors during rheumatoid arthritis frequently reveals N addition. Martin, T., Blaison, G., Levallois, H., Pasquali, J.L. Eur. J. Immunol. (1992) [Pubmed]
  31. The cytoplasmic tail of CD4 is required for inhibition of human immunodeficiency virus type 1 replication by antibodies that bind to the immunoglobulin CDR3-like region in domain 1 of CD4. Benkirane, M., Schmid-Antomarchi, H., Littman, D.R., Hirn, M., Rossi, B., Devaux, C. J. Virol. (1995) [Pubmed]
  32. Characterization of CD4-gp120 activation intermediates during human immunodeficiency virus type 1 syncytium formation. Hart, T.K., Truneh, A., Bugelski, P.J. AIDS Res. Hum. Retroviruses (1996) [Pubmed]
  33. Development of TCRB CDR3 length repertoire of human T lymphocytes. Nishio, J., Suzuki, M., Nanki, T., Miyasaka, N., Kohsaka, H. Int. Immunol. (2004) [Pubmed]
  34. Heavy chain CDR3 optimization of a germline encoded recombinant antibody fragment predisposed to bind the U1A protein. de Wildt, R.M., Ruytenbeek, R., van Venrooij, W.J., Hoet, R.M. Protein Eng. (1997) [Pubmed]
  35. Human anti-idiotypic T cells induced by TCR peptides corresponding to a common CDR3 sequence motif in myelin basic protein-reactive T cells. Zang, Y.C., Hong, J., Rivera, V.M., Killian, J., Zhang, J.Z. Int. Immunol. (2003) [Pubmed]
  36. Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumatoid arthritis. Fitzgerald, J.E., Ricalton, N.S., Meyer, A.C., West, S.G., Kaplan, H., Behrendt, C., Kotzin, B.L. J. Immunol. (1995) [Pubmed]
  37. An echistatin-like Arg-Gly-Asp (RGD)-containing sequence in the heavy chain CDR3 of a murine monoclonal antibody that inhibits human platelet glycoprotein IIb/IIIa function. Deckmyn, H., Stanssens, P., Hoet, B., Declerck, P.J., Lauwereys, M., Gansemans, Y., Tornai, I., Vermylen, J. Br. J. Haematol. (1994) [Pubmed]
  38. What do somatic hypermutation and class switch recombination teach us about chronic lymphocytic leukaemia pathogenesis? Oppezzo, P., Dighiero, G. Curr. Top. Microbiol. Immunol. (2005) [Pubmed]
  39. Complementarity determining region 1 (CDR1)- and CDR3-analogous regions in CTLA-4 and CD28 determine the binding to B7-1. Peach, R.J., Bajorath, J., Brady, W., Leytze, G., Greene, J., Naemura, J., Linsley, P.S. J. Exp. Med. (1994) [Pubmed]
  40. Circulating clonal lymphocytes in myeloma constitute a minor subpopulation of B cells. Chen, B.J., Epstein, J. Blood (1996) [Pubmed]
  41. Analysis of the site of interaction of CD28 with its counter-receptors CD80 and CD86 and correlation with function. Kariv, I., Truneh, A., Sweet, R.W. J. Immunol. (1996) [Pubmed]
  42. Characterization of the response to myelin basic protein in a non human primate model for multiple sclerosis. Uccelli, A., Giunti, D., Mancardi, G., Caroli, F., Fiorone, M., Seri, M., Hauser, S.L., Genain, C.P. Eur. J. Immunol. (2001) [Pubmed]
  43. Development and application of cytotoxic T lymphocyte-associated antigen 4 as a protein scaffold for the generation of novel binding ligands. Hufton, S.E., van Neer, N., van den Beuken, T., Desmet, J., Sablon, E., Hoogenboom, H.R. FEBS Lett. (2000) [Pubmed]
  44. Nodal marginal zone B-cell lymphomas may arise from different subsets of marginal zone B lymphocytes. Conconi, A., Bertoni, F., Pedrinis, E., Motta, T., Roggero, E., Luminari, S., Capella, C., Bonato, M., Cavalli, F., Zucca, E. Blood (2001) [Pubmed]
  45. Transfer of putative complementarity-determining region loops of T cell receptor V domains confers toxin reactivity but not peptide/MHC specificity. Patten, P.A., Rock, E.P., Sonoda, T., Fazekas de St Groth, B., Jorgensen, J.L., Davis, M.M. J. Immunol. (1993) [Pubmed]
  46. Preferential recognition of TCR hypervariable regions by human anti-idiotypic T cells induced by T cell vaccination. Zang, Y.C., Hong, J., Rivera, V.M., Killian, J., Zhang, J.Z. J. Immunol. (2000) [Pubmed]
  47. Optimal design features of camelized human single-domain antibody libraries. Tanha, J., Xu, P., Chen, Z., Ni, F., Kaplan, H., Narang, S.A., MacKenzie, C.R. J. Biol. Chem. (2001) [Pubmed]
WikiGenes - Universities