KIR2DL4, KIR3DL2, KIR3DL3, LILRB1 (ILT2) and LILRB2 (ILT4) variability and haplotypes in a Brazilian population sample from the São Paulo state

Abstract

The Leukocyte Receptors Complex (LRC), which comprehends approximately 1Mb of chromosome 19, is comprised by genes that mostly codify molecules of the Immunoglobulin superfamily (Ig). Among these genes, the Immunoglobulin-like Killer Receptors Family (KIR), expressed on Natural Killer (NK) cells and T cytotoxic lymphocytes, and the Leucocyte Immunoglobulin-like Receptors (LILRs), expressed both on myeloid and lymphoid origin cells, are highlighted. The main ligands of these receptors are the class I HLA molecules from the Major Histocompatibility Complex (MHC), coded by the most variable genes of the human genome. Together, these receptor-ligand complexes are responsible for controlling and modulating the immune responses. The inherent variability of KIR2DL4, KIR3DL2, KIR3DL3, LILRB1(ILT2) and LILRB2(ILT4) genes is poorly explored, although some of these genes seem to be very polymorphic, as reported in previous studies that evaluated only some éxons of these genes. There are no studies describing the variability of these genes in Brazil, which has a highly heterogeneous and admixed population, and is considered a great repository of genetic variability as previously reported in studies characterizing the class I MHC genes. In addition, there is no massive sequencing methodology established to explore the complete variability of these genes. Thus, the aim of this study is to elaborate a strategy to evaluate KIR2DL4, KIR3DL2, KIR3DL3, LILRB1(ILT2) and LILRB2 (ILT4) genes using next generation sequencing and to explore the genetic and haplotypic variability of these genes in a Brazilian sample, correlating the data acquired with the existent variability data of the HLA genes previously evaluated in these same samples. (AU)