T-cell recognition of a chimaeric class II/class I MHC molecule and the role of L3T4

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Abstract
In addition to expressing clonally distributed antigen-specific and major histocompatibility complex (MHC)-restricted receptors, T cells also express non-clonally distributed surface molecules that are involved in T-cell function. Among the most intriguing of the latter are L3T4 and Lyt 2, which are expressed on individual T lymphocytes in striking, though not absolute, concordance with their restriction by either class II or class I MHC determinants1–5, and which are thought to contribute to the overall avidity of T-cell interactions by binding to monomorphic determinants on class II and class I MHC molecules, respectively1–9. To examine the ability of T cells to recognize a single class II domain in the absence of the remainder of the Ia molecule, as well as to evaluate the structural basis for the putative interaction of L3T4 with Ia, a recombinant class II/class I murine MHC gene was constructed and introduced into mouse L cells10. Here we demonstrate that a subset of class II allospecific cytotoxic T lymphocytes (CTL) can specifically recognize and lyse L-cell transfectants expressing an isolated polymorphic Aβ1 domain, and that anti-L3T4 antibody can block such killing, a result inconsistent with the highly conserved membrane-proximal domains of Ia acting as unique target sites for L3T4 binding.