Biomedical subjects

A L Crump

Publications and source records attributed to A L Crump.

6 recordsLinked to original sources

PubMed1994

Variation in expression of MHC class II antigens on horse lymphocytes determined by MHC haplotype.

A panel of monoclonal antibodies was used to characterize the expression of equine Major Histocompatibility Complex (MHC) class II antigens on lymphocytes of horses of different MHC types. MHC class II antigen expression was compared between adult horses and foals, and the level of expression of MHC class II antigens on horse T cell subpopulations was also determined. Peripheral blood lymphocytes (PBL) from young and adult healthy horses of different MHC haplotypes were labeled with the antibodies and assayed by single- and two-color immunofluorescence flow cytometry. A variation in the expression of equine MHC class II antigens on PBL was identified that was determined by MHC haplotype. Both young and old animals carrying the MHC class II haplotype D3 expressed lower levels of MHC class II antigens on their PBL than did horses of other MHC class II types. D3 heterozygotes had an intermediate level of expression. Neonates and foals of any MHC haplotype had lower levels of expression of MHC class II antigens than did adults. MHC class II antigens were identified on surface immunoglobulin positive (sIg+) B cells as well as on T cells, with the B cells staining brightest. Dual staining for MHC class II antigens and markers for equine T cell subsets demonstrated that both EqCD4+ and EqCD8+ T cells expressed MHC class II molecules. These results suggest that the relatively low levels of MHC class II antigen expression on foal and neonate lymphocytes may be developmentally regulated, and not determined by environmental factors. The cause of the low expression of MHC class II antigens linked to the MHC class II haplotype D3 is not known, but it appears to reflect a decreased expression by all lymphocyte subpopulations.

Animals↗

PubMed1993

Thymocyte development in major histocompatibility complex-deficient mice: evidence for stochastic commitment to the CD4 and CD8 lineages.

The mechanism resulting in commitment of precursor cells in the thymus to either the CD4 or CD8 lineage remains poorly understood. In principle, this may reflect a stochastic process or may reflect instructional signals from host major histocompatibility complex (MHC) molecules. We have examined the role of MHC products in subset commitment by using mice deficient in class I or class II MHC products. Normal numbers of committed CD4 intermediates (CD4+ CD8lo) develop in the thymus in the absence of class II molecules. Similarly, CD8 transitional cells (CD4loCD8+) are present in the thymus of mice lacking class I products. These findings suggest that commitment of CD4+8+ precursor cells to either lineage is a stochastic process that does not depend on instructive signals from MHC molecules (i.e., expression of alternative differentiative options by uncommitted precursor cells is independent of this environmental signal). These studies also suggest that an interaction between the T-cell antigen receptor (TCR) and MHC molecules that is independent of CD4/CD8 coreceptor engagement enhances stochastic coreceptor downregulation substantially and leads to upregulation of TCR expression as a prelude to selective events that require joint coreceptor/TCR engagement. We suggest that this initial interaction molds the TCR repertoire of stochastically generated T-cell subsets toward recognition of self-MHC products.

Animals↗

PubMed1993

Immunoregulatory effects of superantigens: interactions of staphylococcal enterotoxins with host MHC and non-MHC products.

Staphylococcus aureus carries a highly conserved set of genes which encode a set of secreted enterotoxins. Although it is likely that these enterotoxins affect the host/parasite in favor of the bacterium, we do not understand the molecular basis of this interaction. We summarize recent evidence that defines two types of interaction between the bacterial toxin and host cellular receptors that may subvert the host immune response to S. aureus. An interaction between the toxin and class II products on APC can result in inhibition of costimulatory activity and thus impair clonal expansion of T cells specific for bacterial antigens. Studies using anti-class II antibodies suggest that this may reflect transmission of a negative signal to APC after ligation of class II products. A second interaction between a subset of toxins, including SEC, with non-MHC products stimulates both T-cell proliferation as well as toxin-specific cytotoxic T cells (CTL). We put forward the hypothesis that this interaction reflects binding of a VCAM-1-like subsequence of SEC to VLA-4 expressed by activated target cells. We suggest that this interaction may serve to inhibit the host response by subversion of lymphocyte homing to sites of infection by SEC-producing staphylococci and by local elimination of (VLA-4+) memory T cells.

Amino Acid Sequence↗

PubMed1988

A monoclonal antibody identifying a T-cell marker in the horse.

A cell surface molecule of equine T lymphocytes was identified and characterized using a mouse monoclonal antibody, HT23A. The molecule was detected on all T cells but not on other cells in peripheral blood, with the possible exception of a small subpopulation (about 5%) of B cells, as assessed by indirect immunofluorescence and flow cytometry. HT23A labelled T cell areas of horse lymph nodes and spleen when used in an indirect immunoperoxidase assay on frozen sections. Macrophages and neutrophils were not labelled by the antibody nor were frozen sections of horse liver, kidney, or brain. HT23A precipitated a molecule of approximately 69 kDa from 125Iodine labelled horse lymphocytes.

Animals↗

PubMed1988

At least two loci encode polymorphic class I MHC antigens in the horse.

Six monoclonal antibodies and ten alloantisera were used to precipitate cell surface molecules of approximately 44 kDa (class I MHC antigens) from radiolabelled equine peripheral blood lymphocytes. All ten antisera were raised against antigens of a single donor horse (horse 0834, ELA-A2,-A2). Four methods of producing antisera were compared: one or two pregnancies, skin allografting, and skin grafting followed by pregnancy. Immunization by pregnancy appeared to produce antibodies against class I products only, while skin grafting raised antibodies to class II antigens as well. Nine of the antisera were raised across an entire MHC haplotype barrier, while one recipient carried the ELA-A2 antigen of the donor. The pregnancy antiserum raised across this barrier probably identifies a second polymorphic class I locus in the horse. Sequential immunoprecipitation using this antiserum in the first stage and an anti-MHC haplotype antiserum or monoclonal antibody reagent in the second stage supported this hypothesis. Gene products of this second ELA class I locus are immunogenic in pregnancy.

Animals↗

PubMed1987

The ELY-1 locus controls a di-allelic alloantigenic system on equine lymphocytes.

The ELY-1 locus controls the expression of a polymorphic cell surface antigen of equine lymphocytes which was detected using antibodies generated by alloimmunization with peripheral blood lymphocytes. The ELY-1 antigens were not detected on erythrocytes or platelets by absorption experiments. The two alleles, which have been designated ELY-1.1 and ELY-1.2, are expressed codominantly and appear to constitute a closed system at the population level. In family studies, the ELY-1 antigens segregated as products of an autosomal locus not linked to the major histocompatibility complex (MHC) of the horse. In the complement mediated lymphocyte microcytotoxicity test, antisera to the ELY-1 antigens selectively killed peripheral blood lymphocytes which did not express surface immunoglobulin. The ELY-1 antigens may be useful markers for equine T cells when assayed in this fashion. Three alloantisera were used in immune precipitation of iodinated and solubilized cell surface proteins from peripheral blood lymphocytes. Electrophoresis of the precipitates in sodium dodecyl sulphate (SDS)-polyacrylamide gels demonstrated strong bands in the Mr 180-190K range that were shared in the three different preparations. These results suggest that the ELY-1 allospecificities are expressed on an equine equivalent of the murine T200 molecule.

Alleles↗