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Indian Marine Gas Turbine (IMGT) division of HAL is engaged in overhaul and repair of Avon and Allision Engines from its customers ONGC and GAIL respectively.
Coincidently, this single amino acid substitution introduced within the CH2 domain of the heavy chain (at position C41 by IMGT codon numbering or 290 by Kabat numbering) of IgG molecule caused the inability of the mutagenized biosimilar rAb to bind to protein A column.
Our analysis reveals that 7.7% (23/300) of our characterized class I alleles contain a previously uncharacterized polymorphism, and another 4.7% (14/300) of the genotyped alleles contain incomplete sequence annotations within IMGT (release 3.22.0).
However, the analyzed sequences are those reported in IMGT, which have been generated as the Immunogenetics community identifies new sequences primarily in the exons and only incidentally in the introns.
Our results, using completely characterized allele sequences from IMGT, indicate differential sequence variability across various genomic features within and across class I HLA alleles.
IMGT, a system and an ontology that bridge biological and computational spheres in bioinformatics.
Immunogenetics sequence annotation: the strategy of IMGT based on IMGT-ONTOLOGY.
mAb Ig subclass [V.sub.H] (a) [V.sub.L] (a) 4-B10 IgG1 IGHV4-1 IGKV6-13 4-D11 IgG1 IGHV2-3 IGKV16-104 4-E3b IgG1 IGHV1-20 or IGHV1-37 IGKV3-12 6-B5 IgG1 IGHV5-6 IGKV19-93 6-B7 IgG1 IGHV5-6 ND (e,f) 6-H5 IgG1 IGHV5-17 IGKV5-48 8-H9 IgG1 IGHV14-3 IGKV6-32 11-E3 IgG1 IGHV1S81 IGKV6-17 mAb Specificity 4-B10 Light chain (Ig[kappa]) (c,d) 4-D11 Light chain (Ig[lambda]) (d) 4-E3b Light chain (Ig[kappa]) (d) 6-B5 FerretIg 6-B7 Heavy chain (IgH) (g) 6-H5 Light chain (Ig[lambda]) (d) 8-H9 Light chain (Ig[lambda]) (c,d) 11-E3 Heavy chain (Ig[gamma]) (c) (a): identified using IMGT V-Quest (see ).
There is no consensus regarding the positions of the nucleotide variation in the HLA-G promoter and 37UTR, mainly because (i) the IMGT/HLA database only presents sequences within 300 bases upstream to the first translated ATG, (ii) the complete 3'UTR gene segment is not considered in the IMGT database, and (iii) several HLA alleles were described presenting only some exon sequences.
Considering the HLA-G coding region (from the first translated ATG to the stop codon), at least 75 single nucleotide polymorphisms (SNP) have been observed, defining the 50 currently described HLA-G alleles, encoding only 16 distinct proteins (IMGT, database 3.14.0, November 2013).
Sequences were also examined in the V-QUEST tool at IMGT database (http://www.imgt.org/), and similar results were achieved.
Selecting target HLAs is another crucial step in epitope-based vaccinology, as an effective preparation has to include protective epitopes capable of binding MHCs in the majority of individuals; the IMGT HLA database (http://www.ebi.ac .uk/ipd/imgt/hla/) provides updated information about HLA alleles and polymorphisms with their relative distribution among the population .
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