Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems be involved virus uptake. Depending on papillomavirus subtype, it has been reported that occurs by clathrin- or caveolin-mediated mechanisms. Regarding type 16 (HPV16), primary etiologic agent for development cervical cancer, clathrin-mediated...

ABSTRACT Infection with various human papillomaviruses (HPVs) induces cervical cancers. Cell surface heparan sulfates (HS) have been shown to serve as primary attachment receptors, and molecules structural similarity cell HS, like heparin, function competitive inhibitors of HPV infection. Here we demonstrate that the N , ′-bisheteryl derivative dispirotripiperazine, DSTP27, efficiently blocks papillomavirus infection by binding HS moieties, 50% inhibitory doses up 0.4 μg/ml. In contrast...

Expansion of the CD8 T-cell memory pool, also known as 'memory inflation', for certain but not all viral epitopes in latently infected host tissues is a special feature immune response to cytomegalovirus. The L(d)-presented murine cytomegalovirus (mCMV) immediate-early (IE) 1 peptide prototype an epitope that associated with inflation. Based on detection IE1 transcripts lungs it was previously proposed episodes gene expression and antigenic activity due desilencing limited number genes may...

The lungs are a noted predilection site of acute, latent, and reactivated cytomegalovirus (CMV) infections. Interstitial pneumonia is the most dreaded manifestation CMV disease in immunocompromised host, whereas immunocompetent host lung-infiltrating CD8 T cells confine infection nodular inflammatory foci prevent viral pathology. By using murine as model, we provide evidence for critical role mast (MC) recruitment protective to lungs. Systemic triggered degranulation selectively infected MC....

The elucidation of the molecular and immunological mechanisms mediating maintenance latency in human tuberculosis aids to develop more effective vaccines define biologically meaningful markers for immune protection. We analyzed granuloma-associated lymphocytes (GALs) from lung biopsies five patients with latent Mycobacterium (MTB) infection. MTB CD4+ CD8+ T cell response was highly focused lung, distinct PBL, as assessed by TCR-CDR3 spectratyping coupled a quantitative analysis TCR VB...

ABSTRACT Both antigen-presenting cells and immune effector are required to effectively eradicate or contain Mycobacterium tuberculosis -infected cells. A variety of cytokines involved ensure productive “cross talk” between macrophages T lymphocytes. For instance, infection with mycobacteria leads effective interleukin-7 (IL-7) IL-15 secretion, both able maintain strong cellular responses α/β γ/δ Here we show that either cytokine is enhance survival M. BALB/c mice significantly compared...

Acute infection with murine cytomegalovirus (mCMV) is controlled by CD8 + T cells and develops into a state of latent infection, referred to as latency, which defined lifelong maintenance viral genomes but absence infectious virus in latently infected cell types. Latency associated an increase numbers epitope-specific over time, phenomenon known “memory inflation” (MI). The “inflationary” subset has been phenotyped KLRG1 CD62L - effector-memory (iTEM). It agreed upon that proliferation iTEM...

Human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation represent candidate targets HPV-specific major histocompatibility complex class I-restricted CD8(+)-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of T-cell repertoire. We identified HLA-A2 binding HPV16 variant peptides from human, bacterial, or viral origin which able to drive directed against wild-type amino...

Abstract Monitoring of CD8+ T‐cell responses in cancer patients during peptide vaccination is essential to provide useful surrogate markers and demonstrate vaccine efficacy. We have longitudinally followed 3 melanoma who were immunized with peptides derived from Melan‐A/MART‐1. Recombinant HLA‐A2 tetramers loaded the naturally presented Melan‐A/MART‐1 nonamer (AAGIGILTV) analog (ELAGIGILTV) used combination phenotypical analysis for different subsets including naive T cells, effector “true...

Cytomegaloviruses (CMVs) are host species-specific in their replication. It is a hallmark of all CMVs that productive primary infection controlled by concerted innate and adaptive immune responses the immunocompetent host. As result, usually passes without overt clinical symptoms develops into latent infection, referred to as "latency". During latency, virus maintained non-replicative state from which it can reactivate under conditions waning surveillance. In contrast, an immunocompromised...

ABSTRACT Antigen-specific T-cell responses may be described by combining three categories: (i) the specificity and effector functions of a population, (ii) quantity (i.e., number responding T cells within CD4/CD8 population), (iii) “quality” (defined receptor [TCR] structure). Several methods to measure are now available including evaluation precursors using limiting dilution, enzyme-linked immunospot assay, ex vivo TCR variable (v)-segment analysis determined flow cytometry, TCR-CDR3 length...

Murine models of cytomegalovirus (CMV) infection have revealed an exceptional kinetics the immune response. After resolution productive infection, transient contraction viral epitope-specific CD8 T-cell pool was found to be followed by a expansion specific for certain epitopes during non-productive ‘latent’ infection. This phenomenon, known as ‘memory inflation’ (MI), based on inflationary KLRG1+CD62L− effector-memory T cells (iTEM) that depend repetitive restimulation. MI gained substantial...

Despite a broad cell-type tropism, cytomegalovirus (CMV) is an evidentially pulmonary pathogen. Predilection for the lungs of medical relevance in immunocompromised recipients hematopoietic cell transplantation, whom interstitial CMV pneumonia frequent and, if left untreated, fatal clinical manifestation human infection. A conceivable contribution to airway diseases other etiology issue that so far attracted little attention. As route primary infection upon host-to-host transmission early...

Cytomegalovirus (CMV) infection is the most critical infectious complication in recipients of hematopoietic cell transplantation (HCT) period between a therapeutic hematoablative treatment and reconstitution immune system. Clinical investigation as well mouse model experimental HCT have consistently shown that timely antiviral CD8 T cells for preventing CMV disease recipients. Reconstitution T-cell lineage generates naïve with random specificities among which CMV-specific need to be primed...

ABSTRACT Several characteristics make human papillomavirus (HPV) amenable to vaccination. Anti-HPV-directed vaccines are based on the observation that HPV E6 and E7 oncoproteins constitutively expressed in HPV-positive cervical cancer may serve as tumor rejection antigens. Five types (16, 18, 31, 33, 45) account for 80% of cancer. Until now, type immune response capable mediating an effective antitumor has not been defined. In order define anticancer-directed situ, we characterized CD4 + CD8...

Abstract CD8 + T cells play a central role in immune protection against infection with Mycobacterium tuberculosis . One of the target epitopes for anti‐ M. directedCD8 is HLA‐A2‐restricted 19‐kDa lipoprotein peptide VLTDGNPPEV. cell clones directed this epitope recognized not only nominal ligand, but also closely related (VPTDPNPPEV) from HIV envelope gp120 (HIV env gp120) protein characterized by IFN‐γ release. This cross‐reactivity was confirmed ex vivo tetramer‐sorted patients and...

Abstract Effective eradication of human papillomavirus (HPV)‐positive tumors may require CD8+ and CD4+ T‐cell‐mediated immune responses. Ectopic expression MHC class II surface molecules has been described in the context cervical cancer, but coexpression with other components antigen presentation pathway not addressed. We have evaluated malignant squamous epithelium HPV+ cancer lesions by situ costaining HLA‐DR CLIP or DMA/DMB. Cervical cells exhibit 3 phenotypes: ( i ) DR+/CLIP+ DM+; ii...

Novel diagnostic tools are needed to diagnose latent infection and provide biologically meaningful surrogate markers define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition the more than 100-year-old tuberculin skin test (TST) for diagnosis of MTB blood. The advent soluble MHC/peptide tetramer molecules allows objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted...

SUMMARY Recent studies have suggested that vaccination induces alterations in the T cell receptor (TCR) repertoire. We investigate diversity of TCR repertoire after immunization with a recombinant hepatitis B surface vaccine seven healthy subjects CD8+ cells peripheral blood lymphocytes. Cellular immune responses were monitored over time by sorting CD8 followed TCR-VA and -VB complementarity determining region 3 (CDR3) analysis. Frequency individual VB families was determined flow cytometry....

Several major histocompatibility complex (MHC) alleles have been reported to present peptides derived from the HPV16 E7 oncoprotein T cells. We describe an overrepresentation of HLA-B8 allele (28.44%) in cervical cancer patients as compared MHC class I frequency a local healthy control population (18.80%) and identification HLA-B8-binding peptide TLHEYMLDL (HPV16 E7(7-15)), which is able drive E7-specific I-restricted T-cell responses peripheral blood lymphocytes individuals....

Cytomegaloviruses (CMVs) are controlled by innate and adaptive immune responses in an immunocompetent host while causing multiple organ diseases immunocompromised host. A risk group of high clinical relevance comprises transiently recipients hematopoietic cell transplantation (HCT) the "window risk" between eradicative therapy malignancies complete reconstitution system. Cellular immunotherapy adoptive transfer CMV-specific CD8 T cells is option to prevent CMV disease controlling a primary...

Human papillomaviruses (HPVs) inflict a significant burden on the human population. The clinical manifestations caused by high-risk HPV types are cancers at anogenital sites, including cervical cancer, as well head and neck cancers. Host cell defense mechanisms such autophagy initiated upon entry. At same time, virus modulates cellular antiviral processes structures promyelocytic leukemia nuclear bodies (PML NBs) to enable infection. Here, we uncover adaptor p62, also known...