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A Berns

Publications and source records attributed to A Berns.

147 records · Page 9Linked to original sources

HLA-restricted recognition of viral antigens in HLA transgenic mice.

Cytotoxic T lymphocytes (CTL) recognize antigen in the context of the class-I products of the major histocompatibility complex (MHC). The extensive polymorphism of class-I molecules is thought to be linked to their capacity to present a large variety of foreign antigens. Whether a single T-cell receptor (TCR) recognizes two separate epitopes (the foreign antigen and an epitope on MHC molecules), or a single epitope resulting from the combination of a foreign antigen and an MHC molecule, has not yet been resolved. In view of the differences between species in primary structure of histocompatibility antigens, it might be predicted that the TCR repertoire would evolve in concert with the diversity of MHC antigens. The mouse and human TCR repertoire would be optimally adapted to engage in productive interactions only with mouse (H-2) and human (HLA) MHC antigens respectively, especially if the more conserved features of histocompatibility antigens, in addition to foreign antigen, were seen by the TCR. Alternatively, only the most variable segments of MHC antigens might be engaged in antigen presentation and thus in interaction with the TCR. In that case, interaction between MHC plus antigen and the TCR might not necessarily be limited by species-specific features. By analysis of the T-cell response against virus-infected cells in HLA-B27/human beta 2-microglobulin double transgenic mice, we report here that the mouse T-cell repertoire is perfectly capable of using the human HLA-B27 antigen as a restriction element.

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Blockage of alpha beta T-cell development by TCR gamma delta transgenes.

T lymphocytes recognize antigens by means of T-cell receptors (TCR) composed of alpha beta or gamma delta heterodimers. The mechanism governing the development of alpha beta- and gamma delta-bearing T cells from a common precursor T cell is so far unknown. It has been proposed that T-cell precursors rearrange their gamma- and delta-chain genes first, and alpha beta T cells are generated only from those cells that fail to rearrange productively both gamma- and delta-chain genes. Our recent study on gamma delta-transgenic mice contradicted this hypothesis, however, and indicated that repression of gamma-chain gene expression mediated by a transcriptional silencer element has a critical role in the generation of alpha beta T cells. Here we report that the generation of alpha beta T cells is severely blocked in transgenic mice carrying gamma- and delta-chain transgenes without the associated silencer, thereby strengthening the validity of the silencer model of T-cell development.

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