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Category: Clinical Microbiology
Antibody Informatics: IMGT, the International ImMunoGeneTics Information System, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555817411/9781555817350_Chap21-1.gif /docserver/preview/fulltext/10.1128/9781555817411/9781555817350_Chap21-2.gifAbstract:
The efficiency of the adaptive immune response and its capability of recognizing a large number of different antigens depend on the huge diversity of the antigen receptors, immunoglobulins (IG), or antibodies of the B lymphocytes and T cell receptors (TR) of the T lymphocytes. The genes that code the IG and TR are highly polymorphic and are organized in clusters in several loci (three loci for IG and four for TR in humans) located on different chromosomes (four in humans) in the genome ( 1 , 2 ). The molecular synthesis of the IG and TR chains is particularly complex and unique. It includes several mechanisms that occur at the DNA level: combinatorial rearrangements of the variable (V), diversity (D), and joining (J) genes that code the IG and TR variable domain, exonuclease trimming at the ends of the V, D, and J genes, and the random addition of nucleotides by the terminal deoxynucleotidyltransferase (TdT) that create the junction N diversity and, for IG, somatic hypermutations ( 1 , 2 ). The IG and TR repertoires show an extraordinary diversity with a potential of 1012 IG and 1012 TR per individual, and the only limiting factor is the number of genetically programmed B and T cells for an organism. Therefore, the analysis of the IG and TR genes and of their expression represents a crucial challenge for the understanding of the immune response in normal and pathological situations.
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IMGT Collier de Perles for V-DOMAIN and C-DOMAIN. A, VH and V-KAPPA. B, CH1 and C-KAPPA. The VH, V-KAPPA, CH1, and C-KAPPA of the motavizumab antibody are shown as examples. IMGT Colliers de Perles are shown on one layer (top), on two layers (middle) (INN, from IMGT/2Dstructure-DB, http://www.imgt.org), and on two layers with hydrogen bonds (bottom) (3ixt_H and 3ixt_L, from IMGT/3Dstructure-DB, http://www.imgt.org) ( 26 , 48 ). In the V-DOMAIN, anchors (positions 26 and 39, 55 and 66, 104 and 118) support the three CDR (CDR1-IMGT, CDR2-IMGT, and CDR3-IMGT that correspond to the BC, C′C″, and FG loops, respectively) ( 29 , 30 , 32 ). The VH and V-KAPPA CDR-IMGT lengths are [10.7.12] and [5.3.9], respectively. In the C-DOMAIN, anchors (positions 26 and 39, 104 and 118) support the BC and FG loops as in a V-DOMAIN, whereas in the absence of a C′ strand, C′C″ loops, and C″ strand, anchors 45 and 77 delimit the CD transverse strand ( 31 , 32 ). A ban symbol indicates an error (K instead of CH1 R120) in the 3D structure PDB file (3ixt), detected by using the IMGT unique numbering and by comparison with the INN sequence. A similar type of error (A instead of CH1 V121) has also been detected by IMGT for the 3D structure of the anti-HIV b12 antibody (1hzh).
IMGT/DomainGapAlign alignments. A, VH and V-KAPPA. B, CH1 and C-KAPPA. The closest V-REGION and J-REGION identified at the amino acid level are aligned with the user sequence (here, motavizumab INN 8693, as example). The VH and V-KAPPA are identified as having 86.9% and 83% identity at the amino acid level with the Homo sapiens IGHV2-70*01 and IGKV1-5*01, respectively (% identity is shown in an upper section online). Amino acid differences are indicated below the V and J alignments. The FR-IMGT and CDR-IMGT, strands and loops are according to the IMGT unique numbering for V domain ( 28 , 29 , 30 , 32 ). The CH1 and C-KAPPA are identified as having 100% identity at the amino acid level with the H. sapiens IGHG1*03 CH1 and IGKC*01, respectively. IMGT/DomainGapAlign displays the C-domain amino acid sequence of the user, with IMGT gaps and delimitations of the strands, turns, and loops, according to the IMGT unique numbering ( 31 , 32 ).
IMGT/3Dstructure-DB Domain pair contacts and IMGT paratope and epitope details. A, IMGT/3Dstructure-DB Domain pair contacts between the VH of motavizumab (3ixt_H) and the Fusion glycoprotein F1 (ligand) (3ixt_P). B, IMGT/3Dstructure-DB Domain pair contacts between the V-KAPPA of motavizumab (3ixt_L) and the Fusion glycoprotein F1 (ligand) (3ixt_P). ‘Polar,’ ‘Hydrogen bonds,’ and ‘Nonpolar’ were selected before display, in ‘Atom contact types.’ Amino acids belonging to the CDR1-IMGT, CDR2-IMGT, and CDR3-IMGT are colored online according to the IMGT color menu (red, orange, and purple, respectively, for VH; blue, green, and green-blue, respectively, for V-KAPPA). In this 3D structure, all but one amino acid that contact the antigen belong to the CDR-IMGT. Clicking on [email protected] gives access to the IMGT [email protected] cards ( 26 , 48 ). C, ‘IMGT paratope and epitope details’ of the IG/Ag complex ‘3ix’t is shown. Each AA that belongs to the IG paratope is characterized by its position in the V domains according to the IMGT unique numbering ( 29 , 30 , 32 ). Thus, ‘A (35V1_A)’ means that the alanine (A) is at position 35 of the V domain 1 of 3ixt_A (VH). In the same way, ‘G(107V1_B)’ means that the glycine (G) is at position 107 of the V domain 1 of 3ixt_B (V-KAPPA). Each AA that belongs to the antigenic determinant (epitope) is characterized by its position (here, position in the chain, in the 3D structure). For example, ‘S (3_C)’ means that the serine (S) is at position 3 of the Fusion glycoprotein F1 ligand (3ixt_C), whereas ‘SN (23-24_C)’ means that the serine (S), asparagine (N) are at positions 23, 24. The ‘IMGT paratope and epitope’ analysis of the IG/Ag 3D structure (3ixt) is from IMGT/3Dstructure-DB (http://www.imgt.org).
List of the IMGT/HighV-QUEST a results files with number of columns and results content