HLA Class I Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic Thais.

Background: Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system.

Objectives: To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness.

Methods: Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed.

Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection.

Immunogenetic surveillance of HIV/AIDS.

Evolutionary pressure by viruses is most likely responsible for the extraordinary allelic polymorphism of genes encoding class I human leukocyte antigens (HLA) and killer immunoglobulin-like receptors (KIR). Such genetic diversity has functional implications for the immune response to viruses and generates population-based variations in HLA class I allele frequencies and KIR gene profiles. The HIV-1 virus has relatively recently established itself as a major human pathogen, rapidly diversifying into a variety of phylogenetic subtypes or clades (A-G) and recombinants in different populations.

Cross-reactivity and expansion of dengue-specific T cells during acute primary and secondary infections in humans.

Serotype-cross-reactive memory T cells responding to secondary dengue virus (DENV) infection are thought to contribute to disease. However, epitope-specific T cell responses have not been thoroughly compared between subjects with primary versus secondary DENV infection. We studied CD8(+) T cells specific for the HLA-A*1101-restricted NS3(133) epitope in a cohort of A11(+) DENV-infected patients throughout acute illness and convalescence.

HLA class II restriction of HIV-1 clade-specific neutralizing antibody responses in ethnic Thai recipients of the RV144 prime-boost vaccine combination of ALVAC-HIV and AIDSVAX(®) B/E.

Immune responses to vaccines may be influenced or associated with allelic variants of host genes such as those encoding human leucocyte antigens (HLA). We have molecularly determined the HLA class II DR and DQ gene, allele and haploype profiles in HIV-1 negative ethnic Thai recipients of an HIV-1 prime boost vaccine regimen, designed to induce neutralizing antibody (NAb) responses to HIV-1 CRF01_AE. Non-response to vaccine associated with DRB1*11 (3/32 responders vs.

Major histocompatibility complex class I-related chain A allele mismatching, antibodies, and rejection in renal transplantation.

Even when kidney allografts are well matched for human leukocyte antigen (HLA) and anti-HLA antibodies are not detected, graft rejection can still occur. There is evidence that some patients who lose their graft have antibodies specific for major histocompatibility complex (MHC) class I-related chain A (MICA) antigens. We investigated whether mismatching MICA alleles associates with MICA antibody production and graft rejection or dysfunction.

Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.

Background: Idiopathic membranous nephropathy is a major cause of the nephrotic syndrome in adults, but its etiologic basis is not fully understood. We investigated the genetic basis of biopsy-proven cases of idiopathic membranous nephropathy in a white population.

Methods: We performed independent genomewide association studies of single-nucleotide polymorphisms (SNPs) in patients with idiopathic membranous nephropathy from three populations of white ancestry (75 French, 146 Dutch, and 335 British patients).

Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross-reactive.

Cross-reactive memory T cells induced by primary infection with one of the four serotypes of dengue virus (DENV) are hypothesized to have an immunopathological function in secondary heterologous DENV infection. To define the T-cell response to heterologous serotypes, we isolated HLA-A(*)1101-restricted epitope-specific CD8(+) T-cell lines from primary DENV-immune donors. Cell lines exhibited marked cross-reactivity toward peptide variants representing the four DENV serotypes in tetramer binding and functional assays.

Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes.

Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors.

TNF and LTA gene, allele, and extended HLA haplotype associations with severe dengue virus infection in ethnic Thais.

Severe dengue virus (DENV) infection is characterized by a cascade of cytokine production, including the production of tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha). We have analyzed a variety of polymorphisms in the TNF and LTA genes of 435 ethnic Thais who had subclinical DENV infection, primary or secondary dengue fever (DF), or primary or secondary dengue hemorrhagic fever (DHF). The TNF -238A polymorphism marking the TNF-4,LTA-3 haplotype occurred in a significantly greater number of patients with secondary DHF (20 [15.

Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.

Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years.

HIV-1 diversity versus HLA class I polymorphism.

HIV-1 is rapidly diversifying in African, Asian and Caucasoid populations, which in parallel display extensive polymorphism of genes encoding class I human leukocyte antigens (HLA). Immune responses mediated by HLA class I molecules are imprinting mutations in HIV-1, which in turn affects HIV-1 diversity. Intra- and inter-ethnic studies have shown reproducible HLA class I allele, haplotype and supertype associations with HIV-1 infection and the development of AIDS (HIV/AIDS).

SNP haplotypes and allele frequencies show evidence for disruptive and balancing selection in the human leukocyte receptor complex.

The human leukocyte receptor complex (LRC) of Chromosome 19q13.4 encodes polymorphic and highly homologous genes that are expressed by cells of the immune system and regulate their function. There is an enormous diversity at the LRC, most particularly the variable number of killer cell immunoglobulin-like receptor (KIR) genes.

A comparison of HLA-DR and -DQ allele and haplotype frequencies in Trinidadian populations of African, South Asian, and mixed ancestry.

Using polymerase chain reaction-sequence-specific primer (PCR-SSP) typing, this study determined the frequency of human leukocyte antigen (HLA) DR- and -DQ alleles and haplotypes in individuals of African (n = 75), South Asian (n = 98), and mixed (n = 102) ancestry from the Caribbean island of Trinidad. We detected 19 different haplotypes containing DRB3, 8 containing DRB4, 6 containing DRB5, and 6 different haplotypes without DRB3/4/5 genes. Twenty-nine haplotypes were identified in Africans, 24 in the South Asians, and 32 in the mixed group.

High resolution molecular phototyping of MICA and MICB alleles using sequence specific primers.

Major histocompatibility complex (MHC) class I chain-related genes, MICA and MICB, are located centromeric to human leukocyte antigen B (HLA-B) on chromosome 6. In response to stress stimuli, MIC is expressed on epithelial, endothelial and fibroblast cells, but not lymphocytes and has been demonstrated to ligate the natural killer (NK) cell receptor, NKG2D. Nucleotide sequences of MICA and MICB are highly polymorphic and several methods have been established to identify these polymorphisms, including sequence-based typing and sequence-specific oligonucleotide probing.

T cell responses to an HLA-B*07-restricted epitope on the dengue NS3 protein correlate with disease severity.

Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects.

A CD45 polymorphism associated with abnormal splicing is absent in African populations.

The CD45 antigen is essential for normal antigen receptor-mediated signalling in lymphocytes, and different patterns of splicing of CD45 are associated with distinct functions in lymphocytes. Abnormal CD45 splicing has been recognized in humans, caused by a C77G transversion in the gene encoding CD45 (PTPRC). Recently the C77G polymorphism has been associated with multiple sclerosis and increased susceptibility to HIV-1 infection.