Regulation of HLA class I expression by non-coding gene variations.

The Human Leukocyte Antigen (HLA) is a critical genetic system for different outcomes after solid organ and hematopoietic cell transplantation. Its polymorphism is usually determined by molecular technologies at the DNA level. A potential role of HLA allelic expression remains under investigation in the context of the allogenic immune response between donors and recipients.

CD8+ T-Cell Repertoire in Human Leukocyte Antigen Class I-Mismatched Alloreactive Immune Response.

In transplantation, direct allorecognition is a complex interplay between T-cell receptors (TCR) and HLA molecules and their bound peptides expressed on antigen-presenting cells. In analogy to HLA mismatched hematopoietic stem cell transplantation (HSCT), the TCR CDR3β repertoires of alloreactive cytotoxic CD8 responder T cells, defined by the cell surface expression of CD137 and triggered by HLA mismatched stimulating cells, were analyzed in different HLA class I mismatched combinations. The same HLA mismatched stimulatory cells induced very different repertoires in distinct but HLA identical responders.

Identification of 3 novel HLA-B alleles: B*08:173, B*18:72:03 and B*53:05:02.

A total of 3 novel human leukocyte antigen-B (HLA-B) alleles were detected by next generation sequencing and confirmed by monoallelic sequencing.

Allorecognition of HLA-C Mismatches by CD8 T Cells in Hematopoietic Stem Cell Transplantation Is a Complex Interplay between Mismatched Peptide-Binding Region Residues, HLA-C Expression, and HLA-DPB1 Disparities.

HLA-C locus mismatches (MMs) are the most frequent class I disparities in unrelated hematopoietic stem cell transplantation (HSCT) and have a detrimental impact on clinical outcome. Recently, a few retrospective clinical studies have reported some variability in the immunogenicity of HLA-C incompatibilities. To get better insight into presumably permissive HLA-C MMs, we have developed a one-way mixed lymphocyte reaction (MLR) assay allowing to quantify activated CD56CD137CD8 lymphocytes in HLA-C incompatible combinations.

High-allelic variability in HLA-C mRNA expression: association with HLA-extended haplotypes.

Human leukocyte antigen (HLA)-C is a clinically relevant transplantation antigen in unrelated hematopoietic stem cell and cord blood transplantation. Furthermore, HLA-C antigens, as ligands for killer immunoglobulin-like receptors expressed on natural killer cells, have a central role in HIV control. Several studies have reported significant correlations between HLA-C mRNA and cell surface expression with polymorphisms in the 5'- and 3'-regions of the HLA-C locus.

Lack of recognition of HLA class I mismatches outside α1/α2 domains by CD8+ alloreactive T lymphocytes: the HLA-B44 paradigm.

Transplantation with hematopoietic stem cells (HSC) from a donor with a single human leukocyte antigen (HLA) mismatch can be proposed to those patients lacking an HLA identical sibling donor or an unrelated donor matched for the HLA-A, -B, -C, DRB1, DQB1 loci. Incompatibilities at HLA classes I and II loci are associated with an increased risk of graft-versus-host disease (GVHD) and mortality, although no consensus exists yet on the relative importance of specific allele disparities on clinical outcome. Donor search algorithms are now complicated by the growing number of new HLA alleles, in particular those that differ outside the peptide-binding site of the HLA molecules.

Transplanted human pancreatic islets after long-term insulin independence.

Long-term insulin independence after islets of Langerhans transplantation is rarely achieved. The aims of this study were to identify the histological and immunological features of islets transplanted in a type 1 diabetic patient who died of a cerebral hemorrhage after >13 years insulin independence. Islets were pooled from two donors with respectively one and five HLA mismatches.

Impact of HLA-DPB1 haplotypes on outcome of 10/10 matched unrelated hematopoietic stem cell donor transplants depends on MHC-linked microsatellite polymorphisms.

Hematopoietic stem cell transplantation (HSCT) with HLA-A, -B, -C, -DRB1, -DQB1 allele matched (10 of 10) unrelated donors is still associated with a significant rate of posttransplantation complications. In order to disclose additional immunogenetic factors, we analyzed the impact of HLA-DPB1 disparities and major histocompatibility complex (MHC)-resident microsatellite polymorphisms in 246 HLA 10 of 10 matched HSCT patients. First we showed that patients with more frequent/conserved HLA haplotypes had a higher 5-year survival (55% ± 18% versus 39% ± 18%, P = .

HLA-B51 and haplotypic diversity of B-Cw associations: implications for matching in unrelated hematopoietic stem cell transplantation.

In unrelated hematopoietic stem cell transplantation (HSCT), human leukocyte antigen (HLA)-C locus incompatibilities occur frequently and are associated with increased risk of posttransplant complications. Because HLA-B51 is associated with a high rate of Cw disparities, we performed a comprehensive four-digit typing analysis of 140 ABCDRB1 B51 genotypes proven by pedigree analysis and 311 unrelated donors selected for 75 B51-positive patients. In addition, 145 A1/Ax-B8/B51-DR3/DRx donors were HLA typed at a high-resolution level and tested for three microsatellite (Msat) polymorphisms located in the HLA class I and III regions.

Vocal dysperiodicities estimation by means of adaptive long-term prediction.

An adaptive formulation of the long-term bidirectional linear predictive analysis is proposed in the context of the acoustic assessment of disordered speech. Vocal dysperiodicities are summarized by means of a signal-to-dysperiodicity ratio (SDR) marker. It is shown that performing an adaptive forward and backward long-term linear prediction of each speech sample and retaining the minimal prediction error energy as a cue of vocal dysperiodicity results in an SDR that correlates with the perceived degree of hoarseness.

Microchimerism after liver transplantation: absence of rejection without abrogation of anti-donor cytotoxic T-lymphocyte-mediated alloreactivity.

Microchimerism (MC) is defined by the persistence of <1% circulating donor cells resulting from cell migration from the graft; MC may play a role in the induction of unresponsiveness to allogeneic tissues, or may be merely the consequence of the graft's acceptance following immunosuppression. To analyze early MC (7 patients) and late MC (12 patients) following a liver transplantation, we designed a sensitive and semiquantitative nested polymerase chain reaction (PCR) protocol based on the detection of incompatible human leukocyte antigen (HLA)-DRB1 donor alleles. MC was measured in multiple PCR samples and expressed as percent positive PCRs / time point.

Estimation of vocal dysperiodicities in disordered connected speech by means of distant-sample bidirectional linear predictive analysis.

The article presents an analysis of vocal dysperiodicities in connected speech produced by dysphonic speakers. The processing is based on a comparison of the present speech fragment with future and past fragments. The size of the dysperiodicity estimate is zero for periodic speech signals.

Risk of chemotherapy-induced pulmonary fibrosis is associated with polymorphic tumour necrosis factor-a2 gene.

In some patients, chemotherapy (CHT) of cancer can result in pulmonary inflammation and fibrosis, eventually leading to respiratory insufficiency. As animal studies have underlined the importance of major histocompatibility complex (MHC) genes in the susceptibility to bleomycin (BLM)-induced pulmonary fibrosis, the authors typed human leukocyte antigen-DR (HLA-DR) and tumor necrosis factor (TNF) genes in patients treated for Hodgkin's disease by a therapy including bleomycin. Patients were divided into pulmonary responders (PR) (n=21) or nonresponders (PNR) (n=20) on the basis of pulmonary alterations detected on chest radiography and the cumulated amount of BLM injected.

Sequence of a new DR12 allele with two silent mutations that affect PCR-SSP typing.

A new HLA-DR12 allele has been identified in a European Caucasoid bone marrow donor. The DRB1*12012 allele differs from DRB1*12011 by two silent substitutions at codons 72 and 78, two polymorphic positions used for DNA subtyping of the DR12 serotype. The co-occurence of the two nucleotide changes is unique to the DR12 group and results in a new PCR-SSP typing pattern.

Polymorphic tumor necrosis factors microsatellite TNFa4 is associated with resistance of Hodgkin lymphoma to chemotherapy and with replapses after therapy.

Background: The response of tumors to chemotherapy (CHT) exhibits wide individual variations.

Patients And Methods: We examined the incidence of polymorphic TNF genes in 61 patients treated for Hodgkin lymphoma.

Results: During treatment, the patients were divided as responders or non-responders, depending upon the amount of CHT required for a clinical eradication of the tumor.

Sequence of a new class I null allele within the HLA-B44 specificity.

A new HLA class I null allele has been identified within the B44 group by combined serological and molecular typing of a blood donor. Based on full-length cDNA sequencing, this novel HLA-B*4419N allele was found to differ from B*4402 by one single base pair deletion at position 7 of exon 1 which results in a stop at codon 19. This mutation was confirmed by polymerace chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) hybridization on genomic DNA.

Sequence of HLA-DRB1*0431 allele.

A novel HLA-DR4 allele has been detected in a volunteer bone marrow donor using a reverse microtiter plate oligotyping assay. Exon 2 cloning and sequencing revealed the new HLA-DRB1*0431 allele which differs from DRB1*0408 by two nucleotide changes at codon 74 leading to an Ala/Leu substitution. Although typical of DR8 alleles, Leu74 polymorphism was not sufficient to confer any serological reactivity with DR8 alloantisera.

HLA and alveolar echinococcosis.

Evidence in animal intermediate hosts that susceptibility to larval infection with Echinococcus multilocularis is restricted to individual host factors prompted us to investigate the susceptibility markers in humans. Because antigens of the extracellular parasite E. multilocularis are possibly presented by MHC molecules in a restricted way, we speculated that MHC polymorphism may influence resistance of the host towards infection and course of disease.

Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom.

Background: Specific immunotherapy with honeybee venom (BV) is highly effective, but allergic side effects can occur during treatment. Immunotherapy with peptides containing major T-cell epitopes of the relevant allergen or allergens provides an alternative strategy without these problems.

Objective: The study investigates the immunologic mechanisms and clinical effects of immunotherapy with T-cell epitope peptides of the major BV allergen, the phospholipase A2 (PLA).

Direct, MHC-dependent presentation of the drug sulfamethoxazole to human alphabeta T cell clones.

T cells can recognize small molecular compounds like drugs. It is thought that covalent binding to MHC bound peptides is required for such a hapten stimulation. Sulfamethoxazole, like most drugs, is not chemically reactive per se, but is thought to gain the ability to covalently bind to proteins after intracellular drug metabolism.

Antigenicity and immunogenicity of multiple antigen peptides (MAP) containing P. vivax CS epitopes in Aotus monkeys.

Using linear synthetic peptides corresponding to the Plasmodium vivax circumsporozoite (CS) protein of the common type, we have identified several T and B-cell epitopes recognized by human individuals. Three T-cell epitopes studied (p6) from the amino, (p11) from the central and (p25) from the carboxyl regions, were widely recognized by lymphocytes of immune donors. A series of six peptides, in addition to p11, representing the central repeat domain of the CS(p11-p17) protein were used in ELISA assays to map the B-cell epitopes of this region.

Cross-reactivity of T cell lines and clones to beta-lactam antibiotics.

To clarify on a molecular level the specific T cell response to haptens like penicillin G, we generated T cell lines and clones from penicillin-allergic patients. Two types of beta-lactam reactivity of T cells could be delineated: one group of patients showed a rather restricted specificity, as the penicillin-elicited T cell lines generated from such donors proliferated only to the stimulating penicillin, but not to other beta-lactam antibiotics nor to cephalosporines, even if the side chain was identical. This indicates that the penicilloyl structure together with the side chain was recognized by these T cells.