Variability of alpha-3, transmembrane and cytoplasmic tail domains of HLA-C and detection of variants that can modify its function

Abstract

The Major Histocompatibility Complex (MHC) is a gene complex that is closely involved with the regulation of the immune system. This complex carries the Human Leukocyte Antigens (HLA), whose greater importance is related to the recognition of what is self or non-self. HLA- C is the least variable gene of polymorphic classical HLA genes and which have lower expression in the tissues except in the maternal- fetal interface, which is the only classical expressed gene. The encoded molecule by this gene has significant role in antigen presentation and NK cell function regulation, which allows association with physiological situations, such as pregnancy, and pathological, such as infectious diseases, autoimmune, inflammatory, cancer and transplant rejection. Its most studied gene portion is the binding groove to antigenic peptides, due to their importance in antigen presentation to cytotoxic T cells. However, other regions of the gene, that are scorned in variability studies, also deserve attention because they influence the signaling and modulation of cytotoxic effector cells, in the anchoring and stability of the molecule in the plasmatic membrane and internalization and recycling of the HLA-C molecule. Thus, in this project, we will explore the genetic variability and haplotype in the region extending from exon 4 to exon 7 of the HLA -C gene, responsible for coding domains ±3, transmembrane and cytoplasmic domains of HLA-C molecule, including adjacent introns, to understand the influence that polymorphisms in these regions may result in the structure and function of the molecule.