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Development of a novel monoclonal antibody that binds to most HLA-A allomorphs in a conformation-dependent yet peptide-promiscuous fashion

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Abstract

Specificity analyses of peptide binding to human leukocyte antigen (HLA)-A molecules have been hampered due to a lack of proper monoclonal antibodies (mAbs) for certain allomorphs, such as the prevalent HLA-A1 for Caucasians and HLA-A11 for Asians. We developed a mAb that recognizes a conformational epitope common to most HLA-A allomorphs. The mAb, named A-1, does not discriminate peptides by amino acid sequences, making it suitable for measuring peptide binding. A stabilization assay using TAP-deficient cell lines and A-1 was developed to investigate the specificity of peptide binding to HLA-A molecules. Regarding the evolution of HLA-A genes, the A-1 epitope has been conserved among most HLA-A allomorphs but was lost when the HLA-A gene diversified into the HLA-A*32, HLA-A*31, and HLA-A*33 lineages together with HLA-A*29 after bifurcating from the HLA-A*25 and HLA-A*26 branchs. The establishment of A-1 is expected to help researchers investigate the peptide repertoire and develop computational tools to identify cognate peptides. Since no HLA-A locus-specific mAb has been available, A-1 will also be useful for analyzing the locus-specific regulation of the HLA gene expression.

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Abbreviations

HLA:

Human leukocyte antigen

PBMC:

Peripheral blood mononuclear cell

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Acknowledgments

We thank Drs. P. Parham, P. Cresswell, M. Takiguchi, G. Nolan, N. Kashiwagi, and J. Strominger for generous gift of cell lines. We also thank Dr. Jun-ichi Miyazaki for providing the pCAGGSneo vector.

Funding

This study was supported by grants from the JSPS, MEXT (16H06498, KU), AMED (JP18lm0203008, KU), Japan.

Author information

Author notes

  1. Rika Fujimoto

    Present address: Research Institute at Kanagawa Cancer Centre, Yokohama, Japan

Authors and Affiliations

  1. Department of Immunology, Kochi University, Kochi, Japan

    Toshihiro Komatsu, Takeyuki Shimizu, Makoto Kanoh, Rika Fujimoto, Motoki Tada, Kaori Machida & Keiko Udaka

  2. Corporate Business Development Division, NEC, Tokyo, Japan

    Tomoya Miyakawa

  3. Department of Evolutionary Studies of Biosystems, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Japan

    Yoko Satta & Yoshiki Yasukochi

  4. Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Japan

    Yoshiki Yasukochi

  5. Japan Manned Space Systems Corporation, Tokyo, Japan

    Motoki Tada

  6. Science Research Center, School of Medicine, Kochi University, Kochi, Japan

    Sayo Kataoka

Authors
  1. Toshihiro Komatsu
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  2. Takeyuki Shimizu
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  3. Makoto Kanoh
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  4. Tomoya Miyakawa
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  7. Rika Fujimoto
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  9. Kaori Machida
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  11. Keiko Udaka
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Corresponding author

Correspondence to Keiko Udaka.

Ethics declarations

This study did not use human specimens. Immunization of mice was conducted following the institutional guideline for animal handling and experiments.

Conflict of interest

The authors in the Department of Immunology at Kochi University have worked in funded collaboration with NEC Co., Ltd., to develop computational platforms for predicting HLA-binding peptides.

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Komatsu, T., Shimizu, T., Kanoh, M. et al. Development of a novel monoclonal antibody that binds to most HLA-A allomorphs in a conformation-dependent yet peptide-promiscuous fashion. Immunogenetics 72, 143–153 (2020). https://doi.org/10.1007/s00251-020-01154-w

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  • DOI: https://doi.org/10.1007/s00251-020-01154-w

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