Biomedical subjects
Publications and source records attributed to C A Janeway.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In the mouse, potent primary in vitro proliferation of T cells can be induced by allelic variants of cell-surface glycoproteins, Ia antigens, the genes for which are located in the I region of the major histocompatibility complex (MHC) on chromosome 17. The only other potent primary proliferative response known is induced by mixing MHC-identical lymphocytes from strains that differ at the locus termed Mls (ref. 1) (for mixed lymphocyte stimulating), which has been mapped to chromosome 1. While it is relatively easy to raise antibodies against Ia antigens, and thus determine both their chemical nature and their role in T-cell stimulation, the nature of the product of the Mls locus has remained obscure. It has been proposed that the Mls locus product is a minor antigen recognized in association with self-Ia antigens, a translocated Ia-like element, or a mitogenic molecule found on the surface of antigen presenting cells (APC). Here, we demonstrate that APCs from mice carrying stimulatory Mls locus alleles present antigen more efficiently to cloned, antigen-specific, Ia-restricted T cells than APCs from mice carrying nonstimulating Mls locus alleles. We propose that the Mls locus does not encode a unique cell-surface antigen at all; we suggest instead that the T-cell proliferative response induced by Mls-locus disparate cells reflects recognition of self-Ia molecules on APCs. If our interpretation is correct, it provides further evidence both for the quantitative nature of self tolerance and for the existence of a distinct recognition site for self-Ia molecules on antigen-specific T lymphocytes.
CD4 is a molecule expressed on the surface of T lymphocytes which recognize foreign protein antigens in the context of class II major histocompatibility complex (MHC) molecules. Recognition of antigen:class II MHC complexes by CD4+ T cells can be inhibited by anti-CD4 (ref. 3). Nevertheless, specific recognition of the antigen:Ia complex is clearly a function of the T-cell receptor, which is composed of CD3 and the variable polypeptides alpha and beta. Thus, it has been proposed that CD4 serves an accessory function in the interaction of CD4+ T cells and Ia-bearing antigen-presenting cells by binding to non-polymorphic portions of class II MHC molecules and stabilizing the cell interaction. Based on our observation that anti-CD4 could inhibit activation of a cloned line of CD4+ T cells by antibodies directed at a particular epitope on the variable region of the T-cell receptor, we have recently proposed that CD4 is actually part of the T-cell antigen recognition complex, physically associated with CD3:alpha:beta. But numerous studies showing that CD3 and CD4 are not stably associated on the T-cell surface would appear to contradict this model. Here we show that anti-T-cell-receptor antibodies can co-modulate expression of the T-cell receptor and CD4, and that the monovalent Fab fragment of such an anti-T-cell-receptor antibody can, in conjunction with bivalent anti-CD4 antibody, generate an activating signal for the T cell. These findings provide further evidence for a physical association of the T-cell receptor complex and CD4.
Explore the source record for details and available documents.
The response to a novel set of T cell mitogens has been analysed and compared to the response to Mls locus differences. These polyclonal T cell activators, staphylococcal enterotoxins A and B, stimulate T cells in a way that requires an antigen-presenting cell bearing class II MHC products and involves the CD4:T cell receptor complex. However, the specificity of MHC recognition by the T cell receptor is lost in this response. Thus, these mitogens produce a response with characteristics similar to that induced by Mls locus differences. These mitogens can be used to analyse the immunobiology of this response, and may help in understanding and identifying the Mls locus product as well.
Explore the source record for details and available documents.