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D J Schendel

Publications and source records attributed to D J Schendel.

At least 19 recordsLinked to original sources
PubMed1992

Cytotoxic T lymphocytes show HLA-C-restricted recognition of EBV-bearing cells and allorecognition of HLA class I molecules presenting self-peptides.

Human CTL have been isolated that show self-restricted recognition of autologous lymphoblastoid cell lines and allorecognition. The lymphoblastoid cell line ligand most likely used a peptide that is expressed in EBV-bearing cells when the virus enters the lytic cycle. This peptide is presented to CD8+ CTL by HLA-Cw7 molecules. The allogeneic ligand recognized on non-EBV-infected cells is composed of a class I glycoprotein and a naturally selected self-peptide. In previous studies we demonstrated that this ligand is determined by two MHC-linked genes: one gene encodes the allogeneic class I molecule whereas the other controls the self-peptide. Despite the use of different peptides and different class I molecules, seemingly equivalent structures are formed that enable these two ligands to function as antigenic mimics of each other. CTL with the same patterns of dual specificity could be isolated from four unrelated donors, indicating that HLA-Cw7 is frequently involved in self-restricted recognition of EBV-harboring cells. Such CTL could help not only to contain lytic virus during a primary infection but also may be maintained life-long to eliminate cells in which reactivated virus appears.

Burkitt Lymphoma↗
PubMed1992

The HLA-A,B "negative" mutant cell line C1R expresses a novel HLA-B35 allele, which also has a point mutation in the translation initiation codon.

The HLA-A,B negative mutant cell line C1R is widely used as a transfection recipient in functional studies of class I MHC genes. It was derived from a normal B cell line, Hmy2, by three rounds of mutagenesis and immunoselection with anti-HLA mAb. Serology characterizes C1R to be negative for the HLA-A2, A3, B35, Bw62, and Cw3 Ag of the parental cell line while retaining expression of HLA-Cw4. We find, however, that CTL specific for HLA-B35 lyse C1R cells, suggesting that expression of HLA-B35 is also retained. To resolve this paradox we examined the expression of HLA-A,B,C genes and proteins in C1R cells. The results are consistent with deletion of the HLA-A3, Bw62, Cw3 haplotype and retention of the HLA-A2, B35, Cw4 haplotype in C1R. Although present, the HLA-A2 gene appears not to be transcribed. As expected, the HLA-Cw4 gene is transcribed and the protein expressed at normal levels. Transcription of the HLA-B35 gene is also normal and comparable to that of HLA-Cw4. However, expression of the HLA-B35 protein is reduced to a few percent of the parental level. Comparison of the nucleotide sequence of B35 alleles from C1R and Hmy2 revealed that reduced translation in C1R is caused by a point mutation (ATG to TTG) in the translation initiation codon. The HLA-B35 allele from C1R and Hmy2 represents a novel subtype, B*3503, differing from B*3501 by replacement of serine by phenylalanine at the peptide binding position 116. This study shows cell surface levels of a class I molecule which are insensitive to lysis by antibody and complement can be readily recognized by alloreactive T cells, further illustrating the relative sensitivity of Ag recognition by T cells.

Alleles↗
PubMed1991

Enhanced expression of HLA-class II molecules on activated human T lymphocytes following treatment with tumor necrosis factor alpha.

Many factors induce or enhance expression of major histocompatibility complex class I and class II molecules on various cell types. Human T lymphocytes are class II negative in the resting state but show expression of class II molecules following activation. We analyzed the modulating capacity of the lymphokines recombinant interferon gamma (rIFN-gamma), interleukin-4 (IL-4), and recombinant tumor necrosis factor alpha (rTNF-alpha) on class II expression in subsets of alloactivated human T lymphocytes. The activated CD4+ T cells expressed all three class II isotypes (DR, DQ, and DP), whereas the cytotoxic CD8+ T-cell lines expressed DR and DP molecules but failed to bind DQ-specific monoclonal antibodies significantly. Treatment with rIFN-gamma and IL-4 had no effect on class II expression on any of the T-cell lines or clones, whereas rTNF-alpha enhanced class II expression in both subsets. rTNF-alpha could modulate expression of all three class II isotypes but, in principle, it appears only to affect ongoing class II synthesis as de novo synthesis of class II molecules with a resultant change in the class II phenotype from DR+ DQ- DP+ to DR+ DQ+ DP+ in the CD8+ T lymphocytes was not observed. No synergic effects of rINF-gamma and rTNF-alpha were observed; this results from the fact that activated T cells express few, if any, receptors of rIFN-gamma.

Antibodies, Monoclonal↗
PubMed1990

On the peptide model of allorecognition: cytotoxic T lymphocytes recognize an alloantigen encoded by two HLA-linked genes.

The peptide model of allorecognition hypothesizes that alloreactive cytotoxic T lymphocytes recognize peptides associated with major histocompatibility complex (MHC) molecules. This study characterizes an unusual alloantigen that is recognized by two human cytotoxic T-cell lines and may represent a complex formed by the association of a naturally selected peptide with an MHC molecule. Family studies demonstrate that both components of the alloantigen are products of MHC-linked genes. One component is a class I molecule most likely encoded by the HLA-B locus. The second component is encoded by an MHC-linked gene that shows a limited polymorphism; whether it represents the product of a second class I gene or of some other MHC gene remains to be determined. These data provide experimental evidence supporting the peptide model of allorecognition in human beings and indicate that some naturally selected peptides involved in allorecognition may be derived from MHC-encoded proteins.

Antibodies, Monoclonal↗
PubMed1989

Differential surface expression of class II isotypes on activated CD4 and CD8 cells correlates with levels of locus-specific mRNA.

Class II molecules are encoded by genes located within the HLA-D region in man. Three major subregions (DR, DQ, and DP) have been identified, each containing several genes encoding the alpha- and beta-chains of the class II heterodimers. In man B lymphocytes constitutively express class II molecules, whereas T lymphocytes express class II molecules only after Ag activation. We have analyzed isotype-specific expression of class II on CD4+ and CD8+ T cell lines and clones derived from one donor after stimulation with allogeneic cells, with the soluble Ag (purified protein derivative of tuberculin), and with mitogen activation by PHA. Class II mRNA transcripts were analyzed in parallel by Northern blot hybridization with DR, DQ, and DP beta-chain-specific cDNA probes. Nearly all activated T lymphocytes expressed DR molecules and variable numbers of DP+ cells were detected in each T cell line or clone, regardless of the mode of Ag activation. DQ molecules were only found on T cell lines or clones of the CD4 phenotype. In contrast two CD8+ cytotoxic T cell lines did not bind DQ-specific mAb although they did express DR and DP molecules. The presence of DR, DQ, and DP mRNA transcripts correlated with the differential patterns of surface expression, indicating that variations in class II cell surface expression among activated T cells may relate to differential gene regulation in these cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

The use of fusion proteins to study HLA-B27-specific allorecognition.

Potential antigenic regions of the various external domains of the HLA-B27 antigen were expressed as fusion proteins in bacterial hosts and analyzed for their ability to induce humoral and cellular responses. Monoclonal antibodies directed against the proteins recognized monomorphic determinants of denatured HLA-antigens, but not B27-antigens expressed by intact lymphocytes. T-cell proliferation and IL-2 secretion were induced with a fusion protein representing regions of the first and second domains around amino acid residue 114. None of the fusion proteins stimulated cytotoxic T-lymphocytes (CTL) in an HLA-specific manner, although several included those amino acid sequences thought to be important for CTL recognition.

Animals↗
PubMed1988

Major histocompatibility complex markers in patients with nomifensine-induced immune hemolytic anemia.

To evaluate a possible role of major-histocompatibility-complex (MHC)-related immune-response genes for the selective production of drug-induced antibodies, HLA class I (ABC), class II (DR, DQ), class III (BF, C2, C4A, C4B) as well as glyoxalase-1 allotypes were investigated in 26 patients with nomifensine-induced immune hemolytic anemia. No statistically significant deviations of MHC antigen frequencies were noted. The possible implications of these findings are discussed.

Adult↗
PubMed1987

Possible male segregation distortion of DR2 haplotypes in narcolepsy patients.

Segregation of disease-associated DR2-linked haplotypes from patients with narcolepsy was studied in 18 German families. Of these, 13 were informative, as transmission could be traced from DR2 heterozygous patients to their healthy offspring. Although the composition of extended haplotypes was equal in males and females, DR2 was transmitted to 78.6% of the offspring by diseased fathers but only to 57.1% by diseased mothers. Compared to an expected 1:1 ratio according to Mendelian segregation this means a statistically significant deviation (p less than or equal to 0.03) for male but not for female patients. In contrast, transmission distortion was not observed with 30 DR2 haplotypes in 27 healthy families. These data represent a new example of male segregation distortion in an HLA-associated disorder.

Female↗
PubMed1986

Triggering of the lethal hit in human cytotoxic T lymphocytes: a functional role for a 103-kDa T cell-specific activation antigen.

A monoclonal antibody (CB.1) is described that defines a new triggering signal for human cytotoxic T lymphocytes (CTL). The antibody precipitates a 103-kDa surface antigen from activated normal human T cells. The antigen is undetectable or present in only low amounts on resting T lymphocytes but its expression increases strongly after activation and proliferation on T4+ and T8+ T lymphocytes. Binding of antibody CB.1 to CTL results in triggering of the lethal hit. This induction of cytotoxicity is dependent on cross-linking of CTL and an Fc receptor-bearing target cell with CB.1 and requires Ca2+ like antigen-specific triggering. CB.1-induced triggering can be specifically inhibited by binding of antibodies to the T8 or T4 molecules on T8+ or T4+ CTL.

Antibodies, Monoclonal↗
PubMed1986

HLA and narcolepsy in a German population.

In this paper the first MHC data including HLA-A, B, C, DR, DQ and complement BF, C4A, C4B determinants in German narcoleptics are presented together with the first family studies in European Caucasoids. 57 out of 58 unrelated patients (98.3%) were positive for DR2 and DQw1, respectively. In contrast to all other reports, one patient with typical signs of narcolepsy was found to be DR2/DQw1 negative. Data showing significant increase in the frequency of B7, and normal frequencies of B35 were discordant with data from Japanese patients. Definition of the extended DR2 linked haplotypes, deduced from 6 families, revealed that 5 out of 12 were DQw1, DR2, BFS, C4B1, C4A3, B7 (Cw7), while 11/12 had DR2, DQw1, BFS, C4A3, C4B1 in common. In one multiple case family two genotypically different DR2 haplotypes were identified in affected siblings. Results from the family study were concordant with a dominant mode of inheritance with incomplete penetrance of a hypothetical disease susceptibility gene.

Complement C4↗