Involvement of Self in the Interactions of Lymphocytes and Target Cells: Some Speculations on the Nature of MHC Restriction

Abstract

Presentation of antigen on the cell surface and in the context of appropriate major histocompatibility complex (MHC)-encoded antigens is apparently a necessary prerequisite for T cell stimulation. It seems likely that murine T cells (with the exception of some suppressors) are unable to respond to stimulation by soluble antigens alone, either by proliferation and secretion of helper factors or by differentiation to cytotoxic effector function. Depending on the function of the responding T cell subset, the appropriate cell surface structures may be encoded in the IA, IE/C (helper), IJ (suppressor), or K, D or L (cytotoxic) region of the MHC. Much of the debate about this MHC restriction phenomenon has been concerned with determining whether T cells recognize, for example, viral antigen with one receptor entity, and MHC antigens with a second (dual recognition) or alternatively, if there is a single receptor specific for some associative interaction between virus and H-2 antigen. The idea that the T cell may express a single, two-chain receptor which recognizes a virus-H-2 complex is claimed by proponents of both models. The concept that, if there are two components to the receptor(s) they must be closely linked, has recently been supported by the experiment of Kappler et al. (1981) who showed that different MHC restriction and antigen specificity patterns did not assort independently following fusion of two T cell clones.