Studies on the interaction of T-cells with major histocompatibility complex class II antigens.
1. Major histocompatibility complex class II antigens have the central role in the immune response of 'presenting' antigenic peptide to CD4+ T-cells. This interaction with a T-cell's receptor may result in activation, but, if recognition occurs without collateral molecular interactions which cause 'co-stimulation', these T-cells will be tolerized. 2. In the light of current interest in muscle cell transplantation, a transformed myoblast, TE671, phenotypically comparable to untransformed cells, transfected to express class II, was studied as a stable model of antigen presentation by muscle cells. These cells failed to activate T-cells but induced tolerance. 3. The DR alpha chain is unusual being the only non-polymorphic classical class II polypeptide, raising the question of its functional contribution. To this end, several single polypeptide constructs were generated with contributions from different class II alpha-chains. On this basis, it was established that DR alpha makes significant contributions to peptide binding and that its alpha 2 domain is also important in T-cell recognition, possibly through CD4 binding. 4. One implication of the lack of polymorphism of DR alpha may be that it has a wider range of pairing partners, possibly including beta chains of different isotypes. To address this, it is planned to use transfectants expressing only a mixed isotype pair to generate T-cell clones in vitro. These reagents would be useful tools to detect whether such mixed pairs exist physiologically. In this paper, the development of a system is described which will allow this question to be addressed.
Warrens
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Department of Immunology, Royal Postgraduate Medical School, London, U.K.
D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002461:Cell Line, Transformed; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007536:Isomerism; D008213:Lymphocyte Activation; D018482:Muscle, Skeletal / Q000276:immunology*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II