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Vaccines (Basel). 2017 Dec 25;6(1). doi: 10.3390/vaccines6010001.

Structural Analysis and Epitope Prediction of MHC Class-1-Chain Related Protein-A for Cancer Vaccine Development.

Vaccines

Tayo Alex Adekiya, Raphael Taiwo Aruleba, Sbonelo Khanyile, Priscilla Masamba, Babatunji Emmanuel Oyinloye, Abidemi Paul Kappo

Affiliations

  1. Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa. [email protected].
  2. Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa. [email protected].
  3. Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa. [email protected].
  4. Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa. [email protected].
  5. Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa. [email protected].
  6. Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria. [email protected].
  7. Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa. [email protected].

PMID: 29295563 PMCID: PMC5874642 DOI: 10.3390/vaccines6010001

Abstract

Major histocompatibility complex class 1 chain-related gene sequence A is a polymorphic gene found at about 46.6 kb centromeric to HLA-B. It encodes a transmembrane protein, which is a non-classical human leukocyte antigen whose expression is normally induced by stress conditions like cancer and viral infections. The expression of MIC-A leads to the activation of NKG2D receptors of natural killer and T cells, leading to the generation of innate immune response that can easily eliminate/cleanse tumour cells and other cells that express the protein. Several bioinformatics and immunoinformatics tools were used to analyse the sequence and structure of the MIC-A protein. These tools were used in building and evaluating modelled structure of MIC-A, and to predict several antigenic determinant sites on the protein. The MIC-A protein structure generated an average antigenic propensity of 1.0289. Additionally, the hydrophilic regions on the surface of the MIC-A protein where antibodies can be attached were revealed. A total of fourteen antigenic epitopes were predicted, with six found in the transmembrane protein topology, and are predicted to play a role in the development of vaccines that can reactivate the functionalities of the MIC-A protein on the surface of cancer cells in order to elicit a desired immune response.

Keywords: 3-D structure; MIC-A; antigenic peptides; bioinformatics; cancer; epitopes; vaccine

Conflict of interest statement

The authors declare no conflict of interests.

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