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Using Bioinformatics Tools for the Sequence Analysis of Immunoglobulins and T Cell Receptors

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1289
  • Abstract
  • Table of Contents
  • Figures
  • Literature Cited

Abstract

 

The huge potential repertoire of 1012 immunoglobulins and 1012 T cell receptors per individual results from complex mechanisms of combinatorial diversity between the variable (V), diversity (D), and junction (J) genes, nucleotide deletions and insertions (N?diversity) at the junctions and, for the immunoglobulins, somatic hypermutations. The accurate analysis of rearranged immunoglobulin and T cell receptor sequences, and the annotation of the junctions, therefore represent a huge challenge. The IMGT Scientific chart rules, based on the IMGT?ONTOLOGY concepts, were the prerequisites for the implementation of the IMGT/V?QUEST and IMGT/JunctionAnalysis tools. IMGT/V?QUEST analyzes germline V and rearranged V?J or V?D?J nucleotide sequences. IMGT/JunctionAnalysis is the first tool that automatically analyzes the complex junctions in detail. These interactive tools are easy to use and freely available on the Web (http://imgt.cines.fr), either separately or integrated.

Keywords: IMGT; immunoglobulin; T cell receptor; rearrangement; immunogenetics; immunoinformatics; junction analysis; sequence diversity; Collier de Perles; variable gene; variable domain; IMGT/V?QUEST; IMGT/JunctionAnalysis

     
 
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Table of Contents

  • IMGT Standardized Rules
  • JUNCTION
  • IMGT/V‐QUEST
  • Conclusion
  • Abbreviations Used in this Appendix
  • Literature Cited
  • Figures
     
 
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Materials

 
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Figures

  •   Figure a0.1W.1 IMGT Collier de Perles. Amino acid numbering is according to the IMGT unique numbering for V‐DOMAIN (Lefranc et al., ). IMGT Collier de Perles of the VH domain of herceptin (1n8z_B, IMGT/3Dstructure‐DB, http://imgt.cines.fr; Kaas et al., ) is shown as an example. The CDR‐IMGT lengths are [8.8.13]. Hatched positions correspond to missing positions according to the IMGT unique numbering. The CDR‐IMGT are limited by amino acids shown in squares, which belong to the neighboring FR‐IMGT. Amino acids are shown using the one‐letter abbreviations (see APPENDIX for definitions). Hydrophobic amino acids and tryptophan (W) found at a given position in more than 50% of analyzed IG and TR sequences are shown in blue on screen. All prolines (P) are shown in yellow on screen. Arrows indicate the direction of the beta sheets strands and their different designations in 3‐D structures.
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  •   Figure a0.1W.2 IMGT/V‐QUEST submission form.
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  •   Figure a0.1W.3 Top of the IMGT/V‐QUEST results page.
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  •   Figure a0.1W.4 IMGT/V‐QUEST Alignment for V‐GENE. IMGT/V‐QUEST provides the alignment of the input sequence with the five closest V genes and alleles of the IMGT/V‐QUEST reference directory set. The IMGT/LIGM‐DB accession number (identical to the DDBJ/EMBL/GenBank accession number), the IMGT gene name, and the IMGT allele name are indicated for each reference sequence. V‐gene and allele names are according to the IMGT nomenclature (Lefranc, ,b; Lefranc and Lefranc, ,b). Dashes indicate nucleotide identity. Dots indicate gaps according to the IMGT unique numbering (Lefranc et al., ) or nucleotides that are not taken into account for the alignment.
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  •   Figure a0.1W.5 IMGT/V‐QUEST Alignment for D‐GENE and Alignment for J‐GENE. IMGT/V‐QUEST provides the alignment of the input sequence with five close D genes and alleles (see text) and with the five closest J genes and alleles of the IMGT/V‐QUEST reference directory set. The IMGT/LIGM‐DB accession number, the IMGT gene name, and the IMGT allele name are indicated for each reference sequence. D and J gene and allele names are according to the IMGT nomenclature (Lefranc, ,b; Lefranc and Lefranc, ,b). Dashes indicate nucleotide identity. Dots indicate gaps or nucleotides that are not taken into account for the alignment.
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  •   Figure a0.1W.6 IMGT/V‐QUEST Results of IMGT/JunctionAnalysis. The JUNCTION comprises the sequence from amino acid 2nd‐CYS (C) (or codon) at position 104 to amino acid J‐TRP (W) (or codon) at position 118. The CDR3‐IMGT comprises the sequence from amino acid (or codon) 105 to amino acid (or codon) 117. Detailed results are described in the text.
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  •   Figure a0.1W.7 IMGT/V‐QUEST “Translation.” The translation of the V‐REGION of the input nucleotide sequence is displayed with the amino acids (codons) according to the IMGT unique numbering (Lefranc et al., ), with the delimitations of the FR‐IMGT and CDR‐IMGT, and aligned with the most similar V‐REGION sequence from the IMGT/V‐QUEST reference directory set. Dashes indicate nucleotide identity. Dots indicate gaps according to the IMGT unique numbering. Nucleotide mutations are indicated. Amino acid changes are displayed for non‐silent mutations.
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  •   Figure a0.1W.8 IMGT/V‐QUEST “V‐REGION mutation table.” The nucleotide mutations and the amino acid changes are described, by FR‐IMGT and by CDR‐JMGT, according to the rules for the “IMGT description of mutations” (IMGT Scientific chart, http://imgt.cines.fr).
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Literature Cited

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   Lefranc, M.‐P. 2000b. Nomenclature of the Human T Cell Receptor Genes. In Current Protocols in Immunology (J.E. Coligan, B.E. Bierer, D.E. Margulies, E.M. Shevach, and W. Strober, eds.) pp. A.1O.1‐A.1O.23. John Wiley & Sons, Hoboken, N.J.
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   Lefranc, M.‐P., Giudicelli, V., Kaas, Q., Duprat, E., Jabado‐Michaloud, J., Scaviner, D., Ginestoux, C., Clément, O., Chaume, D., and Lefranc, G. 2005a. IMGT, the international ImMunoGeneTics information system. Nucl. Acids Res. 33:D593‐D597.
   Lefranc, M.‐P., Clément, O., Kaas, Q., Duprat, E., Chastellan, P., Coelho, I., Combres, K., Ginestoux, C., Giudicelli, V., Chaume, D., and Lefranc, G. 2005b. IMGT‐Choreography for Immunogenetics and Immunoinformatics. In Silico Biol. 5:45‐60.
   http://www.bioinfo.de/isb/2004/05/0006/.
   Lefranc, M.‐P., Pommié, C., Kaas, Q., Duprat, E., Bosc, N., Guiraudou, D., Jean C., Ruiz, M., Da Piedade, I., Rouard, M., Foulquier, E., Thóuvenin, V., and Lefranc, G. 2005c. IMGT unique numbering for immunoglobulin and T cell receptor constant domains and IG superfamily C‐like domains. Dev. Comp. Immunol. 29:185‐203.
   Letovsky, S.I., Cottingham, R.W., Porter, C.J., and Li, P.W. 1998. GDB: The Human Genome Database. Nucl. Acids Res. 26:94‐99.
   Pommié, C., Sabatier, S., Lefranc, G., and Lefranc, M.‐P. 2004. IMGT standardized criteria for statistical analysis of immunoglobulin V‐REGION amino acid properties. J. Mol. Recognit. 17:17‐32.
   Pruitt, K.D. and Maglott, D.R. 2001. RefSeq and LocusLink: NCBI gene‐centered resources. Nucl. Acids Res. 29:137‐140.
   Ruiz, M. and Lefranc, M.‐P. 2002. IMGT gene identification and Colliers de Perles of human immunoglobulins with known 3D structures. Immunogenetics 53:857‐883.
   Safran, M., Chalifa‐Caspi, V., Shmueli, O., Olender, T., Lapidot, M., Rosen, N., Shmoish, M., Peter, Y., Glusman, G., Feldmesser, E., Adato, A., Peter, I., Khen, M., Atarot, T., Groner, Y., and Lancet, D. 2003. Human Gene‐Centric Databases at the Weizmann Institute of Science: GeneCards, UDB, CroW 21 and HORDE. Nucl. Acids Res. 31:142‐146.
   Sakano, H., Huppi, K., Heinrich, G., and Tonegawa, S. 1979. Sequences at the somatic recombination sites of immunoglobulin light‐chain genes. Nature 280:288‐294.
   Satow, Y., Cohen, G.H., Padlan, E.A., and Davies, D.R. 1986. Phosphocholine binding immunoglobulin Fab McPC603. An X‐ray diffraction study at 2.7A. J. Mol. Biol. 190:593‐604.
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   Yousfi Monod, M., Giudicelli, V., Chaume, D., and Lefranc, M.‐P. 2004. IMGT/JunctionAnalysis: The first tool for the analysis of the immunoglobulin and T cell receptor complex V‐J and V‐D‐J JUNCTIONs. Bioinformatics 20:I379‐I385.
Key References
   Lefranc and Lefranc, 2001a. See above.
   These two books are the prime references for all functional and ORF immunoglobulin and T cell receptor genes and alleles in humans. Genes and alleles are classified and described according to the IMGT Scientific chart rules, based on the IMGT‐ONTOLOGY concepts. Corresponding sequences have been used for the setting up of the IMGT reference directory sets used by IMGT/V‐QUEST and IMGT/JunctionAnalysis.
   Lefranc and Lefranc, 2001b. See above.
Internet Resources
   http://imgt.cines.fr
   Web site of IMGT
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