Frances L. Owen

Relationship of the genes for Chediak-Higashi syndrome (beige) and the T-cell receptor [gamma] chain in mouse and man

The genetic linkage of Chediak-Higashi syndrome and its murine analog, beige (bg), to the T-cell receptor (TCR-gamma) gamma chain gene is further defined. Previous studies using recombinant inbred strains of mice demonstrated that the murine bg gene is genetically linked to a murine TCR-gamma gene. We report that in the mouse the frequency of recombination between these two markers is 0.025. Further, we tested the hypothesis that these two genes are linked in the human genome by analyzing restriction fragment length polymorphisms (RFLPs) in five families with children afflicted with Chediak-Higashi syndrome. In three families, RFLPs in TCR-gamma genes were inherited discordantly from Chediak-Higashi syndrome, demonstrating nonlinkage. We postulate that there is an evolutionary chromosomal breakpoint between the bg gene and the TCR-gamma gene.

Freshly isolated Thy-1+ dendritic epidermal cells express T cell receptor γδ-CD3

Abstract Within murine epidermis exists a population of Thy-1 + DEC which express membrane Thy-1 antigen, but lack CD8 or CD4 antigen. We examined freshly obtained non-cultured Thy-1 + DEC both by immunofluorescence and by biochemical techniques to identify the protein products of the T cell receptor (TCR) and the associated CD3 complex on these cells. Virtually all of the Thy-1 + DEC are brightly positive in CD3 expression with immunofluorescence using the monoclonal antibody 145-2C11. By immunoprecipitation, using this same antibody and polyclonal anti-TCR-γ antibody, the only TCR heterodimer detected on the freshly isolated Thy-1 + DEC is the γδ heterodimer. These findings suggest that in the phenotype and TCR expression, Thy-1 + DEC are analogous to CD8 − , CD4 − early fetal thymocytes.

Neoplastic model for the differentiation of a subpopulation of lymphocytes bearing IgH-1-linked gene products.

A cluster of genes on Chromosome 12 in the mouse genome codes for a series of T cell alloantigens which are acquired sequentially in the development of the T lymphocyte lineage. The position of the genes distal to the immunoglobulin locus has led to extensive speculation as to the role of the product of these genes. Recent results suggest monoclonal antibodies specific for these determinants also react with antigen-specific suppressor factors. Antibodies to determinants we named Tpre, Tthy, Tind. and Tsu (Owen & Riblet 1984) and others (Tokuhisa & Taniguchi 1982) called CT bind the antigen specific chains of suppressor molecules from cells in the immune regulatory circuit implied by the biological nomenclature. Molecules recognized by monoclonal antibodies bear no similarity to those described for either the a or f̂ chains ofthe histocompatability restricted receptor on T lymphocytes (Kappler et al. 1981, AlUson et al. 1982, Chien et al. 1984). Cell lines which bear the putative histocompatibility receptor are largely devoid of the immunoglobuUn-Iinked T cell determinants; most II-2 dependent T cell lines examined failed to express these antigenic determinants, although a cell line which violates this generalization has been found.

Differential Expression of Igh-1 -Linked T-Cell Alloantigens

The relationship between antigen receptors on T and B cells has long been debated(1–3) Immunoglobulin on the surface of B cells clearly acts as an antigen recognition structure(4) and may also be a key to the differentiation of an IgM-bearing early B cell(5) to a cell population expressing both IgM and IgD.(6–7) T- and B-cell receptors may closely resemble one another in that at least part of the polypeptide chain coding for antigenic specificity of each cell type carries determinants cross-reactive with the major serum idiotypes (reviewed in Ref. 8). Although the VH gene products expressed on T and B cells may overlap, (9,10) the fine specificity of the repertoire may not be identical(11,12) The constant-region markers (isotypes) on B cells have never been found to be expressed on the surface of T cells.(13)