Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

Cellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s) within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection.

Missingness in the T1DGC MHC fine-mapping SNP data: association with HLA genotype and potential influence on genetic association studies.

Aim: The absence or 'missingness' of single nucleotide polymorphism (SNP) assay values because of genotype or related factors of interest may bias association and other studies. Missingness was determined for the Type 1 Diabetes Genetics Consortium (T1DGC) Major Histocompatibility Complex (MHC) data and was found to vary across the region, ranging up to 11.1% of the non-null proband SNPs, with a median of 0.

Association of MHC SNP genotype with susceptibility to type 1 diabetes: a modified survival approach.

Aim: The Major Histocompatibility Complex (MHC) is a highly polymorphic region on chromosome 6 encompassing the human leucocyte antigen (HLA)-DQ/DR loci most predictive of susceptibility to type 1 diabetes (T1D). To assess the contribution of other MHC genes, in this exploratory analysis of Type 1 Diabetes Genetics Consortium (T1DGC) family data we characterize association between susceptibility and MHC single nucleotide polymorphism (SNP) genotype, with an emphasis on effects of genetic variation additional to carriage of predisposing or protective MHC haplotypes.

Methods: We use Cox regression analyses of age of onset, stratified by family, to jointly test both linkage and association.

Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression.

Variation in the host response to infection by pathogens including HIV-1 may be conferred by polymorphic genetic factors such as HLA and killer immunoglobulin-like receptors (KIR) genes. Here, we examined KIR and HLA genotype effects on pretreatment viral load, rate of CD4(+) T-cell decline and progression to AIDS among adult HIV-1-infected patients within the Western Australian HIV Study Cohort. In this study, carriage of KIR genes within the 'B' haplotype (eg KIR2DS2) was specifically associated with a more rapid CD4(+) T-cell decline over time and progression to AIDS.

Associations between KIR epitope combinations expressed by HLA-B/-C haplotypes found in an HIV-1 infected study population may influence NK mediated immune responses.

The Killer Ig-like receptors (KIRs) on NK cells regulate NK activity via the recognition of specific HLA class I products on the surface of target cells. To investigate the level at which these genetically polymorphic receptors and ligands influence HIV-1 disease progression, we examined the effect of KIR and HLA genotype on HIV outcome. We observed a significant association between particular combinations of KIR epitopes expressed by HLA-B/-C haplotypes and propose that the repertoire of KIR epitopes expressed by HLA-B and HLA-C alleles within the context of particular haplotypes may be an important component of the NK mediated immune response to HIV and/or other infectious pathogens.

Leukocyte Ig-like receptor complex (LRC) in mice and men.

Here, we compare the architecture of membrane receptors with extracellular Ig-like domains located within the leukocyte Ig-like receptor complex (LRC) of humans and mice. The receptors can be classified broadly into four groups, based on the homology of their Ig-like domains and gene architecture. Receptors in the first group are characterized by the presence of the Ig constant type 2-1 (IgC2-1) and variant Ig (vlg) domains, and include the leukocyte Ig-like receptors (LILRs) and murine paired Ig-activating receptors (PIRs).