T-cell recognition of antigen and the Ia molecule as a ternary complex

T-lymphocyte co-recognition of antigen and major histocompatibility complex (MHC)-encoded molecules (such as murine Ia molecules) is thought to be mediated by a single cell-surface receptor, although the molecular mechanism by which this occurs is controversial (reviewed in ref. 1). One possibility is that the antigen molecule and the Ia molecule interact physically, either before or after encountering the T-cell antigen-specific receptor. Alternatively, both molecules could bind to the receptor independently of one another, accounting for the dual specificity of the receptor without postulating a physical interaction between a limited number of Ia molecules present in any given animal and the myriad antigens to which T cells can respond. Here, we used a recently described approach for analysing the relative avidity of the T-cell receptor for different ligands to address these two possibilities. We describe a T-cell clone whose response to a single antigen, presented in the context of two different Ia molecules, strongly suggests that the antigen and the Ia molecule interact physically.