SNP discovery and molecular evolution in Anopheles gambiae, with special emphasis on innate immune system

<p>Abstract</p> <p>Background</p> <p><it>Anopheles </it>innate immunity affects <it>Plasmodium </it>development and is a potential target of innovative malaria control strategies. The extent and distribution of nucleotide diversity in immunity genes might provide insights into the evolutionary forces that condition pathogen-vector interactions. The discovery of polymorphisms is an essential step towards association studies of susceptibility to infection.</p> <p>Results</p> <p>We sequenced coding fragments of 72 immune related genes in natural populations of <it>Anopheles gambiae </it>and of 37 randomly chosen genes to provide a background measure of genetic diversity across the genome. Mean nucleotide diversity (π) was 0.0092 in the <it>A. gambiae </it>S form, 0.0076 in the M form and 0.0064 in <it>A. arabiensis</it>. Within each species, no statistically significant differences in mean nucleotide diversity were detected between immune related and non immune related genes. Strong purifying selection was detected in genes of both categories, presumably reflecting strong functional constraints.</p> <p>Conclusion</p> <p>Our results suggest similar patterns and rates of molecular evolution in immune and non-immune genes in <it>A. gambiae</it>. The 3,214 Single Nucleotide Polymorphisms (SNPs) that we identified are the first large set of <it>Anopheles </it>SNPs from fresh, field-collected material and are relevant markers for future phenotype-association studies.</p

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Data from: Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function

When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8+ T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for HLA-I alleles such as HLA-B35:01, peptide-deficient (empty) heterodimers are thermostable and detectable on the cell surface. Additionally, peptide-deficient HLA-B35:01 tetramers preferentially bind CD8 and to a majority of blood-derived CD8+ T cells via a CD8-dependent binding mode. Further functional studies reveal that peptide-deficient conformers of HLA-B35:01 do not directly activate CD8+ T cells, but accumulate at the immunological synapse in antigen-induced responses, and enhance cognate peptide-induced cell adhesion and CD8+ T cell activation. Together, these findings indicate that HLA-I peptide occupancy influences CD8 binding affinity, and reveal a new set of regulators of CD8+ T cell activation, mediated by the binding of empty HLA-I to CD8