Complexity of T cell receptor recognition sites for defined alloantigens.

An ultrastructural analysis of human cytotoxic T lymphocyte-target cell (CTL-TC) interaction has been undertaken to enable a better understanding of the killing mechanism. Attention was focused on granules in the CTL, which are known to contain lethal compounds. Within the membrane-delimited cytotoxic granule an electron-dense core as well as numerous membrane vesicles were identified. In CTL-TC conjugates, specific membrane interactions take place, allowing the formation of intercellular clefts into which the granule cores and internal vesicles are released. T cell surface membrane molecules known to be involved in CTL-TC interaction (T cell receptor, CD3 and CD8) are present on the membranes of the granule cores and internal vesicles, facing outward. An explanation for this localization of the membrane may be found in the fact that the granule is connected with an endocytotic pathway. Moreover, the lumen of the granule is rich in the enzyme cathepsin D, which indicates an association with a lysosomal compartment. Exocytosed vesicles and cores are seen to adhere to the plasma membrane of the TC. Although the exact contents of the granule vesicles and core remain to be identified, we suggest that specific interaction of CTL membrane molecules on the cytolytic granule components with molecules on the plasma membrane of the TC may ensure the unidirectional delivery of the lethal hit.

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Molecules relevant for T cell‐target cell interaction are present in cytolytic granules of human T lymphocytes

Peters¹,

Geuze²,

Donk³

et al. 1989

Eur J Immunol

227

146

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Murine macrophage precursor characterization. II. Monoclonal antibodies against macrophage precursor antigens

et al. 1990

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The aim of the present study was the phenotypical analysis of early stages in macrophage (M phi) differentiation. For this purpose, we produced a panel of syngeneic rat hybridomas, which secreted antibodies (mAb) against M phi precursor antigens. As immunogens we used immortalized M phi precursors (P.J. M. Leenen et al., Eur. J. Immunol. 1990, 20: 15). We screened the obtained mAb in the following in vitro models of M phi differentiation: (a) a panel of M phi cell lines ordered in a linear differentiated sequence; (b) immature and mature mononuclear phagocytes obtained from bone marrow (BM) culture; (c) a panel of M phi precursor hybrids, and (d) differentiated and control M phi precursor hybrid cells. Four mAb, ER-MP12, ER-MP20, ER-MP54 and ER-MP58, were selected. These mAb recognize antigens which disappear in the course of M phi differentiation. Next, we investigated whether these mAb also recognized M phi precursors in normal BM. For this purpose, ER-MP-positive and -negative BM fractions were isolated using a fluorescence-activated cell sorter. Fractions were cultured in M phi-colony-stimulating factor-containing conditioned medium, and the resulting mature M phi progeny was quantified using the MTT assay. The present experiments indicate that ER-MP12 and ER-MP20 detect a subpopulation of BM M phi precursors, whereas ER-MP58 stains virtually all M phi precursors. Biochemical analysis of radioiodinated antigens revealed that these mAb recognize different molecules. ER-MP12 and ER-MP20 bound to single-chain (glyco)proteins of 140 kDa and 14 kDa, respectively. ER-MP54 precipitated multiple polypeptides, of which the major chains have an apparent molecular mass of 90, 80-85 and 70-75 kDa. Based on the molecular mass of the recognized antigens and the mAb specificities we conclude that ER-MP12, ER-MP54 and ER-MP58 recognize hitherto unknown antigens of murine M phi precursor cells. The antigen detected by ER-MP20 is most likely identical to Ly-6C.

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T‐cell antigen receptor beta‐chain variable region families: A study of their distribution in normal and reactive tissues

Clark

Boylston

1989

The Journal of Pathology

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The beta chain of the T-cell antigen receptor is constructed using a variable region gene from one of approximately 20 variable gene families. Antibodies that react with the products of these gene families have been used to demonstrate clonal proliferation of T cells. Here, we describe the expression of two beta-chain variable region families in normal and reactive lymphoid tissues. In all the tissues studied, expression was scattered throughout the T-cell areas, without any clustering of expression.

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Complexity of T cell receptor recognition sites for defined alloantigens.

Cited by 27 publications

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Molecules relevant for T cell‐target cell interaction are present in cytolytic granules of human T lymphocytes

Molecules relevant for T cell‐target cell interaction are present in cytolytic granules of human T lymphocytes

Murine macrophage precursor characterization. II. Monoclonal antibodies against macrophage precursor antigens

T‐cell antigen receptor beta‐chain variable region families: A study of their distribution in normal and reactive tissues

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