A5011003972- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Influenza Virus Research Studies
- Food Allergy and Anaphylaxis Research
- Immunodeficiency and Autoimmune Disorders
- Pediatric health and respiratory diseases
- Immune responses and vaccinations
- Alcoholism and Thiamine Deficiency
- Infectious Encephalopathies and Encephalitis
- Viral-associated cancers and disorders
- HIV Research and Treatment
- IL-33, ST2, and ILC Pathways
- Viral gastroenteritis research and epidemiology
- High Altitude and Hypoxia
- Animal Virus Infections Studies
- Mitochondrial Function and Pathology
- interferon and immune responses
- Transgenic Plants and Applications
- Reproductive System and Pregnancy
- Preterm Birth and Chorioamnionitis
- Polyomavirus and related diseases
- Respiratory viral infections research
- Viral Infections and Outbreaks Research
Baylor College of Medicine
2014-2022
Texas Children's Hospital
2014-2022
University of Massachusetts Chan Medical School
2006-2017
Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a of viral susceptibility. cells develop from hematopoietic stem cells, few monogenic errors that specifically interrupt development have been reported. Here we described biallelic mutations IRF8, which encodes an interferon regulatory factor, cause familial deficiency results disease. Compound heterozygous or homozygous IRF8 3 unrelated families resulted paucity mature CD56dim increase the...
Abstract In this study, we demonstrate complex networks of CD8 T cell cross-reactivities between influenza A virus and EBV in humans lymphocytic choriomeningitis vaccinia mice. We also show directly that cross-reactive cells mediate protective heterologous immunity Subsets populations reactive with one epitope cross-reacted either several other epitopes encoded by the same or virus. Human specific to EBV-encoded BMLF1280–288 could be two epitopes. Mouse virus-encoded a11r198–205 three...
Abstract Memory T cells cross-reactive with epitopes encoded by related or even unrelated viruses may alter the immune response and pathogenesis of infection a process known as heterologous immunity. Because challenge virus epitope react only subset cell repertoire in epitope-specific memory pool, vigorous be narrowly focused, oligoclonal. We show this article, examining human cross-reactivity between HLA-A2–restricted influenza A virus-encoded M158–66 (GILGFVFTL) dissimilar Epstein-Barr...
ABSTRACT Fifty years after the discovery of Epstein-Barr virus (EBV), it remains unclear how primary infection with this leads to massive CD8 T-cell expansion and acute infectious mononucleosis (AIM) in young adults. AIM can vary greatly severity, from a mild transient influenza-like illness prolonged severe syndrome. We questioned whether unique HLA-A2.01-restricted, cross-reactive response between influenza A-M1 58 (IAV-M1) EBV BMLF1 280 (EBV-BM) could modulate immune play role determining...
Abstract Long oligopeptides (>10 residues) are generated during the catabolism of cellular proteins in cytosol. To be presented to T cells, such peptides must trimmed by aminopeptidases proper size (typically 8–10 stably bind MHC class I molecules. Aminopeptidases also destroy epitopes trimming them even shorter lengths. Bleomycin hydrolase (BH) is a cytosolic aminopeptidase that has been suggested play key role generating I-presented peptides. We show BH-deficient cells from mice...
The CD8 T cell memory response to the HLA-A2-restricted influenza epitope M1(58-66) can be an instructive model of immune a nonevolving frequently encountered pathogen that undergoes clearance. This repertoire complex, composed large number clonotypes represented at low copy numbers, while maintaining focus on use VB17 receptors with identified Ag recognition motifs. Such structure might provide panoply whose differential avidity for would allow responses under varying antigenic loads....
T cell development in the thymus produces multiple lineages of cells, including innate cells. Studies mice harboring alterations TCR signaling proteins or transcriptional regulators have revealed an expanded population CD4(+) cells that produce IL-4 and express transcription factor promyelocytic leukemia zinc finger (PLZF). In these mice, produced by CD4(+)PLZF(+) leads to conversion conventional CD8(+) thymocytes into resembling memory expressing eomesodermin. The expression PLZF, signature...
Severe infections with Histoplasma capsulatum are commonly observed in patient secondary immunodeficiency disorders. We report a two and half years old boy previously healthy disseminated cutaneous histoplasmosis. Using whole exome sequencing, we found an indel mutation at the CD40LG gene, suggesting diagnosis of hyper-IgM (HIGM) syndrome, even absence usual features for disease. Interestingly, lives region endemic The unusual our case suggest that children severe histoplasmosis resident...
Dendritic cells are important mediators in the early presentation of antigen and regulation differentiation T cells. Peanut oral immunotherapy (POIT) results desensitization most peanut allergic individuals (responders), but not others due to reactions (non-responders). Delineation immunologic changes contributing would help clarify POIT mechanism action. We analyzed dendritic 15 pediatric subjects (5–12 years) undergoing a phase 1 single-center study. examined at baseline, 6-, 12-, 18-...
Abstract During EBV-associated IM influenza A-specific crossreactive memory T cells are activated and play a role in disease severity. In HLA-A2+ patients, M158 (IAV-M1)-specific CD8 cell responses cross-reacted with two different EBV lytic epitopes, BMLF-1280 (17/29) BRLF-1190 (19/20). Furthermore, 11/22 patients demonstrated some intra-viral cross-reactivity between EBV-BRLF1 -BMLF1 responses. Disease severity of did not correlate viral load, but instead directly correlated significantly...
During EBV-associated IM IAV-specific crossreactive memory T cells are activated and play a role in disease severity. In HLA-A2+ patients, influenza M1-58 (IAV-M1)-specific CD8 cell responses crossreacted with two different EBV lytic epitopes, BMLF1-280 (17/29) BRLF1-109 (19/20). Furthermore, 11/22 patients demonstrated some intra-viral crossreactivity between EBV-BRLF1 -BMLF1 responses. Disease severity of directly correlated significantly increased frequencies IAV-M1/EBV-BMLF1, IAV-M1,...
Abstract During EBV-associated infectious mononucleosis (IM) IAV-specific crossreactive memory T cells are activated and play a role in disease severity. In HLA-A2+ IM patients, influenza M158 (IAV-M1)-specific CD8 cell responses crossreacted with two different EBV lytic epitopes, BMLF1280 (17/29) BRLF1109 (19/20). Disease severity of directly correlated significantly increased frequencies IAV-M1/EBV-BMLF1, IAV-M1, EBV-BMLF1 specific cells, mean viral load over the first 5 weeks infection....
Abstract For unknown reasons 5-10% of middle-aged adults (>35 years) remain EBV-sero-negative when the virus infects vast majority people, and is actively shed at high titers during chronic infection. Here we show that (EBV-SN) HLA-A2+ possess a unique IAV-M158-66(GIL) memory CD8 T cell response cross-reacts with EBV lytic epitopes. The five tested EBV-SN had significantly increased tetramer+ frequency compared to adult sero-positive donors. Upon exposure antigens in vitro both IAV-...