T cells can distinguish between allogeneic major histocompatibility complex products on different cell types

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Abstract

In the response of T cells to foreign antigens, the ligand for the T cell α/β receptor is presented on a cell surface as a fragment of antigen complexed to one of the membrane molecules encoded in the major histocompatibility complex (MHC)1–5. The receptor apparently interacts via its variable elements (Vβ, Dβ, Jβ, Vα and Jα) with residues within both the antigen and MHC portion of the ligand. The frequency of T cells responding to a conventional antigen plus self MHC is usually quite low, presumably reflecting the relative rarity of receptors with the particular combination of variable elements to match the antigen/MHC ligand. T cells also respond to allogeneic forms of MHC molecules in the absence of added antigen6. In this case the frequency of responding T cells is very high. One hypothesis to explain this observation is that, in the absence of foreign antigen, MHC molecules are complexed to a large array of peptides derived from self-proteins7. In this case the combination of the polymorphic MHC amino acid residues and many different self peptides presents so many possible ligands that the likelihood of recognition by a given T cell receptor is quite high. The recent crystallography experiments which revealed a dramatic binding cleft on the face of a human MHC molecule5 have given impetus to this view, but as yet there is no direct supporting evidence. We have recently described a close association between murine T cell receptors utilizing the Vβ17a element and reactivity to various allogeneic forms of the murine MHC molecule, I-E (ref. 8). In this paper, we show that this I-E ligand is detected on B cells, but not on I-E+ macrophages or fibroblasts expressing a transfected I-E gene. These results strongly suggest a B cell specific product combines with I–E to form the allogeneic ligand for Vβ17a+ receptors and thus support the concept of alloreactivity described above.

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