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.

Highlights

  • Cancer is one of the most common and widely diagnosed diseases around the world

  • Its expression in cancer cells has been shown to be responsible for the innate immune activities triggered by NK cells and T cells against abnormal growth

  • The primary structure of the MIC-A protein showed that leucine is the most abundant amino acid, making up approximately 9.40% of the total amino acids in the primary sequence followed by glycine, serine and threonine, which have equal amounts of amino acid residues (7.60%)

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Summary

Introduction

Cancer is one of the most common and widely diagnosed diseases around the world It is caused by unusual cell growth or cell division and has the ability to invade or spread to other parts of the body from the point of tumour formation (otherwise known as primary tumours). Different therapies on how to combat this deadly disease has been built on developing prognostic and predictive tools based on the status of lymph nodes, the size and grade of tumour, hormone receptors, and human epidermal growth factor receptor 2 (HER2) expression [2]. These therapies have been considered ineffective in treating cancer. Certain actions of the immune system may lead to the detection of tumour cells during tumour formation, which can lead to the abolishment and cleansing of tumours [3,4]; though tumour cells may display various characteristics which make it difficult for the immune system to recognize them due to their unstable genetic nature [5]

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