Non-covalent presentation of @entity207 to @entity1 XXXX + T cells is independent of distinct human leucocyte antigen-bound peptides.

@entity1 @entity404 @entity1358 @entity3303 @entity56 @entity1598 @entity207
BACKGROUND: It has been shown that drugs comprise a group of non-peptide antigens that can be recognized by @entity1 T cells in the context of HLA class II and that this recognition is involved in @entity56 . Recent studies have demonstrated a MHC-restricted but processing- and metabolism-independent pathway for the presentation of allergenic drugs such as @entity3303 and @entity207 ( @entity1598 ) to drug-specific T cells. However, there is little information so far on the precise molecular mechanisms of this non-covalent drug presentation. OBJECTIVE: The aim of this study was to evaluate the requirements for a specific peptide occupying the groove of the MHC class II molecule for the efficient presentation of non-covalently bound drugs to @entity404 + T cells. METHODS: We analysed the effect of coincubation or prepulse of @entity1358 ( @entity1358 ) with different peptides on the proliferative responses of @entity1598 -specific @entity404 + T cell clones. In a second series of experiments, we eluted HLA-bound peptides from the surface of @entity1358 by mild acid treatment. Successful removal of peptides was tested directly using labelled peptides and functionally by monitoring activation and proliferation of peptide-specific T cell clones. Finally, the presentation of @entity1598 to @entity1598 -specific T cell clones before and after elution of MHC class II bound peptides was tested. RESULTS: We found that neither peptide coincubation nor peptide prepulse of @entity1358 altered the proliferative response of @entity1598 -specific T cells. @entity1358 treated with the acid for a short time retained cell viability, MHC class II expression and antigen presenting cell function. However, defined peptides could be eluted from surface MHC class II molecules nearly quantitatively. Nevertheless, the chemically non-reactive drug @entity1598 could still be presented to specific T cells independent of the presence of distinct self-peptides. CONCLUSION: Our data suggest that small molecules like drugs can bind to a multitude of HLA-bound peptides or that, similar to superantigens, they might bind directly to HLA.
