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

Grant number: 16/03622-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): June 01, 2016
Effective date (End): February 28, 2018
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal Investigator:Erick da Cruz Castelli
Grantee:Michelle Almeida da Paz
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


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.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LIMA, THALITTA H. A.; SOUZA, ANDREIA S.; PORTO, IANE O. P.; PAZ, MICHELLE A.; VEIGA-CASTELLI, LUCIANA C.; OLIVEIRA, MARIA LUIZA G.; DONADI, EDUARDO A.; MEYER, DIOGO; SABBAGH, AUDREY; MENDES-JUNIOR, CELSO T.; et al. HLA-A promoter, coding, and 3 ` UTR sequences in a Brazilian cohort, and their evolutionary aspects. HLA, v. 93, n. 2-3, p. 65-79, . (16/03622-0, 13/17084-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PAZ, Michelle Almeida da. HLA-C alpha-3, transmembrane and citoplasmic tail domains variability and detection of functional variants. 2018. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.

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