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Updated: Jun 14, 2026
Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
Published on: October 15, 2021
Description and molecular modeling of two novel HLA alleles: HLA-A*0343 and A*0345
Sara Frison1, Pietro Crivello, Elena Longhi
1Dipartimento di Medicina Rigenerativa, Immunologia dei Trapianti di Organi e Tessuti-Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena, Milan, Italy.
Insights
Two novel human leucocyte antigen (HLA) variants, HLA-A*0343 and HLA-A*0345, were identified in Caucasian individuals. These discoveries may impact peptide binding and transplantation compatibility.
Area of Science:
- Immunogenetics
- Molecular Biology
- Human Genetics
Background:
- Human leucocyte antigen (HLA) genes are crucial for immune response and transplantation.
- Novel HLA variants can influence immune recognition and disease susceptibility.
Purpose of the Study:
- To report the identification and characterization of two new human leucocyte antigen (HLA) variants.
- To analyze the potential functional impact of these novel HLA alleles.
Main Methods:
- DNA sequencing was used to identify novel HLA alleles.
- Amino acid substitutions were analyzed using molecular modeling.
- The potential impact on peptide binding and protein interactions was assessed.
Main Results:
- Two novel HLA alleles, HLA-A*0343 and HLA-A*0345, were identified in Caucasian individuals.
- HLA-A*0343 exhibits amino acid substitutions affecting the F pocket charge, potentially altering peptide repertoire.
- HLA-A*0345 has an amino acid substitution in the alpha3 domain, with no predicted significant impact on beta2-microglobulin or CD8 interaction.
Conclusions:
- The identified HLA variants expand the known HLA allele database.
- HLA-A*0343 may have functional implications for immune response due to alterations in peptide binding.
- Further studies are needed to fully elucidate the clinical significance of these novel HLA alleles, particularly for HLA-A*0345 in transplantation contexts.
Abstract:
We report the identification of two novel human leucocyte antigen (HLA) in two Caucasian individuals. HLA-A*0343 differs from A*03010101 by four changes at nucleotides 411-414 (CCGG-->TGAA) and by a point mutation at position 418 (G-->C). These differences lead to two amino acid substitutions at codon 114, where arginine has changed into negatively charged glutamic acid, and at codon 116, where aspartic acid has changed into positively charged histidine. Molecular modeling showed that these changes have a profound influence on the overall charge of the F pocket of the groove, resulting in potentially important changes in the peptide repertoire. HLA-A*0345 was found in a hematological female patient candidate to bone marrow transplantation. This new variant differs from HLA-A*03010101 at position 845 (C-->A) encoding an amino acid change of threonine to asparagine at codon 258 located in the alpha3 domain. Molecular modeling does not suggest a substantial role of this substitutions on the interaction with beta2-microglobulin or CD8.
