Killer Cell Inhibitory (Ig-like) Receptor (KIR) and Immunoglobulin-like transcript 5 (ILT 5) genes of human Chromosome 19: Genotyping and role in the susceptibility to genetic atopy and asthma

Erwin Schrödinger Fellowship J 1912 Role of KIRs an ILTs in genetic atopy and asthma Christoph GASSNER 06.03.2000 Natural Killer Cell Ig-like receptors (KIRs) and Immunoglubin-like transript (ILT) genes of human chromosome 19y13.2-4 are monitroing the espression of Major Histocompatibility Complex (MHC) class I. The huge polymorphism at the KIR locus is caused by (1) an allelic polymorphism and (2) individually different genetic combinations of the KIR multi-gene locus. The Immunoglobin Like Transcripts (ILTs) are structually related to the KIRs, but their pressence on B cells and monocytes suggests that the control of immune responses as seen in NK cells may be extended to other cell types. In contrast to the arrangement of KIR genes, all the ILT genes seem to present in one individual. However, a serious allelic variation among one of these genes was found - ILT5 is characterized by a striking diversity. Pattern of clustering and segretation analysis in asthma families have suggested a genetic component to asthma and atopy. A linkage wirh the chromosomal region 19q13 is described. Because of their chromosomal localisation, but also their molecular characteristics and functional properties KIRs and ILTs seem to be likely candidates in playing a role in the pathogenesis of asthma and atopy. A PCR based DNA typing system has been developed using sequence specific priming technique (SSP) to identify specific KIR haplotypes, KIR genes and their broad allelic variants. The applicant plans to investigate genomic DNA of an appropriate number of asthma affected individuals with the KIR and - yet to develop - ILT5 genotyping system. This study might result in the definition of contributing genes and explanation of their role in susceptibility to, but also help the choice of targets for therapeutic intervention in genetic asthma.