Studies on the Interaction of T-Cells with Major Histocompatibility Complex Class II Antigens

Abstract

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.

Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity

“…Being inactivated, we hypothesized that the virions are not capable of replicating and, thus, will not lead to antigen presentation on HLA-Class I molecules. Instead, the inactivated virus should behave as extracellular proteins generally do: After pinocytosis and lysosomal processing they will end up being presented on HLA Class II molecules, stimulating CD4 cells [ 46 ]. If so, the inactivated virus would be ideal for testing the entire virus-specific CD4 cell repertoire, because all the proteins are presented and the respective MHC molecules expressed by the individual test subjects will define which determinants of the virus are displayed to CD4 cells for recognition.…”