Biomedical subjects

S Porcelli

Publications and source records attributed to S Porcelli.

24 records · Page 2Linked to original sources

PubMed1989

Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes.

Human cluster-of-differentiation 1 (CD1) is a family of cell surface glycoproteins of unknown function expressed on immature thymocytes, epidermal Langerhans cells and a subset of B lymphocytes. Three homologous proteins, CD1a, b and c, have been defined serologically, and the CD1 gene locus on human chromosome 1 contains five potential CD1 genes. Analysis of the predicted amino-acid sequences of CD1 molecules reveals a low but significant level of homology to major histocompatibility complex (MHC) class I and class II molecules, and, like MHC class I molecules, CD1 molecules are associated non-covalently with beta 2-microglobulin. These structural similarities to known antigen-presenting molecules, together with the expression of CD1 on cells capable of antigen presentation, suggest a role for CD1 molecules in antigen recognition by T cells. Here we demonstrate the specific recognition of CD1a by a CD4-CD8- alpha beta T-cell receptor (TCR) expressing cytolytic T lymphocyte (CTL) line and the specific recognition of CD1c by a CD4-CD8- gamma delta TCR CTL line. The interaction of CD1-specific CTLs with CD1+ target cells appeared to involve the CD3-TCR complex, and did not show evidence of MHC restriction. These results suggest that for a subset of T cells, CD1 molecules serve a function analogous to that of MHC class I and II molecules.

Antibodies, Monoclonal↗

PubMed1989

Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system.

A direct quantitative and phenotypic cytofluorographic analysis of TCR-gamma/delta+ lymphocytes as well as an immunohistologic study of their tissue distribution and microanatomy was made possible by the availability of two mAbs (anti-TCR-delta 1 and anti-C gamma M1) specific for framework determinants on human TCR gamma and delta chains, respectively. TCR-gamma/delta+ lymphocytes, ranging between greater than 0.5 and 16% of CD3+ cells, were found in fetal and postnatal thymus, fetal and adult peripheral lymphoid organs, and adult peripheral blood. While TCR-gamma/delta+ lymphocytes comprised a small subpopulation of T cells (mean, approximately 4%) occasionally greater than 10-16% of CD3+ cells expressed TCR-gamma/delta. Virtually all TCR-gamma/delta+ thymocytes/lymphocytes expressed CD7, CD2, and CD5 but were heterogeneous with respect to their expression of CD1, CD4, CD8, CD28, CD11b, CD16, and Leu-7. Human TCR-gamma/delta+ cells populate both organized lymphoid tissues (thymus, tonsil, lymphnode, and spleen) as well as the gut- and skin-associated lymphoid systems at similar frequencies without obvious tropism for epithelial microenvironments. TCR-gamma/delta+ lymphocytes tend to be located within a given organ wherever TCR-alpha/beta+ lymphocytes are found. This study shows that TCR-gamma/delta+ lymphocytes constitute a small but numerically important, phenotypically diverse T cell population distributed throughout the body. These results support the concept that TCR-gamma/delta+ cells comprise a distinct, functionally heterogeneous, mature T cell sublineage that may substantially broaden the T cell repertoire at all immunologically relevant sites.

Antibodies, Monoclonal↗

PubMed1989

Effect of oligosaccharide chain length, exposed terminal group, and hapten loading on the antibody response of human adults and infants to vaccines consisting of Haemophilus influenzae type b capsular antigen unterminally coupled to the diphtheria protein CRM197.

Vaccines consisting of oligosaccharide (OS) derived from Haemophilus influenzae type b capsular polysaccharide and conjugated to carrier proteins had been shown capable of eliciting memory-type capsular polysaccharide of H. influenza type b antibody responses in human infants, but the structural variables governing immunogenicity were not defined. Here a series of conjugates were made with the diphtheria protein CRM197 and with uniterminally coupled OS haptens that varied in chain length, exposed terminal residue, or multiplicity of loading as defined by ribose/protein ratio. Adults were given a single injection, 1-yr-old infants were given a two-injection sequence, and capsular polysaccharide of H. influenzae type b antibody responses were assessed by radioantigen binding. Vaccines C-4r, C-6r, and C-12r, in which ribitol-ended OS of mean length 4, 6, or 12 repeat units were coupled at low hapten loading, were about equally immunogenic (geometric means 2 to 5 micrograms/ml in infants, 5 to 9 micrograms/ml in adults). Vaccine C7p was made with a higher loading of OS having mean length 7 repeat units and having mainly phosphate monoester at the exposed termini Vaccine C-7R was made from a portion of C-7p by enzymatic removal of most of the terminal phosphates. Compared to the C-4r, C-6r, and C-12r series, vaccines C-7p and C-7R induced geometric means about 10-fold higher in adults and 20-fold higher in infants. Thus OS chain length (in the range studied) and exposed terminus are less critical variables in this system than the extent of hapten loading.

Adult↗

PubMed1987

Immunochemical variables affecting radioantigen-binding assays of antibody to Haemophilus influenzae type b capsular polysaccharide in childrens' sera.

In radioantigen-binding assays for antibody to Haemophilus influenzae type b capsular polysaccharide, an apparent antibody concentration [( (["Ab"]) is assigned to test sera on the basis of binding equivalence to dilutions of standard adult antiserum. In childrens' sera, ["Ab"] can disagree between laboratories and between intralaboratory assays using different preparations of radioantigen. Immunochemical variables causing disagreement include the dilution of test serum at which ["Ab"] is assigned and the concentration and size distribution of radioantigen. Binding-dilution curves of many childrens' sera displayed shallower slopes than did the standard, thus ["Ab"] increased with dilution, particularly in low-binding sera. An increase in radioantigen concentration also raised ["Ab"]. Using larger-sized radioantigen raised the binding in standard and childrens' sera comparably and thus would not directly affect ["Ab"] but would raise ["Ab"] indirectly by increasing the serum dilution. These results are theoretically predicted if the affinity of childrens' antibodies are lower than that of the standard.

Antibodies, Bacterial↗

PubMed1983

Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells.

Two antisera and a monoclonal antibody raised in BALB.K mice against cloned, major histocompatibility complex (MHC)-restricted, antigen-specific helper T cell lines are described. These antibodies are specific for individual cloned T cell lines and are potent inducers of T cell proliferation. The induction of T cell proliferation by these antibodies requires the presence of an adherent accessory cell. There is no H-2 restriction between this accessory cell and the cloned T cell, nor is this antibody-induced proliferation blocked by a monoclonal anti-Fc receptor antibody. The requirement for an accessory cell, however, is eliminated in the presence of an IL-1- or IL-2-rich supernatant. Thus this system allows the analysis of helper T cell activation with only a single cell type present. Anti-T cell sera also induce T cell-dependent B cell proliferation and immunoglobulin secretion. The induction of T cell-dependent B cell activation by these sera does not require H-2-matched T cells and B cells. The specificity of these antibodies and their ability to stimulate cloned helper T cells in the absence of antigen and antigen-presenting cells strongly suggest that these antibodies are directed against antigen and/or Ia recognition sites on the T cell.

Animals↗

PubMedDate not supplied

Human T cells expressing an invariant V alpha 24-J alpha Q TCR alpha are CD4- and heterogeneous with respect to TCR beta expression.

A population of mature CD4-CD8-double-negative T cells that expresses an invariant Valpha24-JalphaQ TCR has been identified in humans; the majority of these cells appear to express Vbeta11. A closely related in variant TCRalpha chain is also expressed by a population of NK1+ murine T cells, but these cells may be either CD4+ or double negative. In this report, multiple CD4+ or double-negative Valpha24+Vbeta11+ T-cell clones were isolated, and only the double-negative clones were found to express the invariant TCRalpha chain. Studies of TCRbeta chains expressed by these cells demonstrate that a subset in some donors use Vbeta genes other than Vbeta11. Characterization of Vbeta11 TCRs in one donor by CDR3-length analysis was also carried out. The results indicate that multiple Vbeta11 TCRs of differing CDR3 lengths may associate with the invariant TCRalpha chain.

CD4 Antigens↗