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    The purpose of this research is to identify and characterize deleterious genetic variants in the co-stimulatory ligand B7-1, also known as the human cluster of differentiation CD80 marker. The B7-1 ligand and the major histocompatibility complex class II (MHC II) molecules are the main determinants that provide B-cells the required competency to act as antigen presenting cells. For this, participation of both MHC class II molecules and CD80 is required. The interaction of the CD80 ligand with CD28 on the surface 7 of TH cells plays a key role in the activation of TH cells and progression of B cells through the S phase, hence, leading to their proliferation in mitosis. A set of 2313 genetic variants in the B7-1 ligand have been mapped and retrieved from dbSNP database. Subsequently, 150 non-synonymous single nucleotide polymorphisms (nsSNPs) were mapped and subjected to the sequence and structural homology based predictions, which were further analyzed for protein stability and the disease phenotypes. Finally, we identified 7 potentially damaging nsSNPs in the B7-1 ligand that may affect its interaction with the cognitive receptor CD28, hence, may also interfere with TH cell activation and B cell proliferation. We propose that subsequent experimental analyses (stability, expression and interactions) on these proteins can provide a deep understanding about the effect of these variants on the structure and function of CD80. Copyright © 2020 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

    Citation

    Riya Mathur, Loveena Sharma, Bhanupriya Dhabhai, Athira M Menon, Amit Sharma, Narendra Kumar Sharma, Tikam Chand Dakal. Predicting the functional consequences of genetic variants in co-stimulatory ligand B7-1 using in-silico approaches. Human immunology. 2021 Feb;82(2):103-120

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    PMID: 33358455

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