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We have studied memory in T cell receptor (TCR) transgenic mice expressing a Db-restricted TCR specific for the male peptide (H-Y). CD8 + T cells from female TCR transgenic C57BL/6 (B6) mice were activated by transferring them Into X-irradiated male (B6 x bm12)F1 hybrid recipients. Subsequently, they were highly purified by cell sorting and transferred for various lengths of time into female...
High endothelial venules (HEV) in lymphoid tissues support high levels of lymphocyte extravasion from the blood. We purified high endothelial cells from human tonsils by immunomagnetic selection with MECA79 MAb to construct an HEV cDNA.library. Differential screening of this library using cDNA probes from HEV (plus) or flat-walled vessel (minus) endothelial cells allowed us to characterize a novel...
Major histocompatibility complex class II molecules bind and present to T cells fragments of protein antigens entering the endocytic pathway. Using normal B lymphoblasts, we have combined metabolic pulse-chase labeling, high resolution organelle fractionation, and immunoprecipitation to examine class II trafficking and antigen loading in a physiological model system. Most newly synthesized class II-invariant...
The IL-2 receptor (IL-2R) consists of three subunits, the IL-2Rα, IL-2Rβ, and IL-2Rγ chains. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2Rβ and IL-2Rγ, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here, we report that Syk protein tyrosine kinase (PTK) Is physically associated with IL-2R in peripheral...
We previously identified possible intermediates in V(D)J recombination at the TCRδ locus and characterized molecules with signal ends and with covalently sealed (hairpin) coding ends in thymocytes of scid mice by Southern blotting. Here, we use a sensitive ligation-mediated PCR assay to demonstrate that all coding ends detected in acid thymocytes are covelently sealed. Neither coding nor signal ends...
Mice immunized against a cancer recognize antigens unique to that cancer, but the molecular structures of such antigens are unknown. We Isolated CD4 + T cell clones recognizing an antigen uniquely expressed on the UV-induced tumor 6132A; some clones inhibited the growth of tumors bearing the specific antigen. A T cell hybridoma was used to purify this antigen from nuclear extracts by RP-HPLC...
Class I MHC expression by target cells inhibits lysis mediated by natural killer (NK) cells, often in an allele-specific fashion. It has been proposed that NK cell inhibitory receptors recognize complexes of class 1 molecules with specific cellular peptides that define self, displacement of which would render cells NK sensitive. By loading the mostly empty Dd class I molecules of cell lines deficient...
Motheaten viable (me v ) mice are deficient in the cytosolic protein tyrosine phosphatase, PTP1C, and exhibit severe B cell immunodeficiency and autoantibody production. The role of PTP1 C in B cell selection and function was analyzed by breeding immunoglobulin transgenes specific for a defined antigen, hen egg lysozyme, into ma v mice. Antigen triggered a greater and more rapid elevation...
Direct and indirect cytopathic mechanisms have been proposed to account for the loss of CD4 + T cells after infection with human immunodeficiency virus type 1 (HIV-1). We report here that HIV-1 infection of the human thymus in vivo results in thymocyte depletion by at least two different mechanisms. Thymocytes within multiple stages of differentiation are induced to die of apoptosis; most...
The increased affinity of memory antibody responses is due largely to the generation and selection of memory B cells that accumulate somatic mutations after initial antigenic stimulation. Further affinity maturation and mutation also accompany subsequent immunizations. Previous studies have suggested that, like primary antibody-forming cell (AFC) clones, secondary AFC do not accumulate further mutations...
Using a fluorescein-conjugated antigenic peptide, peptide-receptive H-2K b MHC class I molecules were found throughout the secretory pathways of RMA cells and peptide transporter (TAP)-deficient derivative cells (RMA/S). RMA/S cells displayed higher levels of intracellular peptide-receptive molecules, while, surprisingly, RMA cells expressed 3- to 5-fold more cell surface peptide-receptive...
CD8 + T cells control immune responses, and recent studies suggest that this regulation is, in part, specifically directed towards TCR structures expressed by CD4 + cells. To develop a system to study the role of the TCR in regulatory interactions, we isolated clones of CD4 + cells expressing identified TCR Vβ chains. These CD4 + clones were used to stimulate and expand...
Several tumor antigens are recognized by autologous cytolytic T lymphocytes (CTL) on human melanoma MZ2-MEL. Some of them are encoded by genes MAGE-1 and MAGE-3, which are not expressed in normal tissues except in testis. Here, we report the identification of a new gene that codes for another of these antigens. This gene, named BAGE, codes for a putative protein of 43 aa and seems to belong to a family...
Interactions mediated by TCRs expressed on different T cell subsets may play a role in immunoregulation. To investigate this idea, we studied the regulation of superantigen-induced TCR Vβ-restricted responses. We asked whether the in vivo regulation of CD4 + Vβ8 + T cells following SEB injection is controlled by CD8 + T cells. We found that in mice deficient in CD8 + ...
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