Ever since the discovery of specific immune response (Ir) genes in the I regions of the major histocompatibility complex (MHC) of mammals (1), certain characteristic features of the phenomena they control presented a considerable challenge:

  1. H-linked Ir gene control has been observed only for thymus-dependent antigens that are proteins or polypeptides, and is concerned with T cell responses such as the stimulation of delayed-type hypersensitivity (DTH) and specific helper T cells (1, 2).

  2. The specificity of Ir gene function is remarkable and distinguishes readily between antigens with different amino acid primary sequences (3–6). This has been demonstrated for synthetic antigens and also for native antigens. It is nevertheless remarkably distinct from the specificity of the T cell responses themselves (7), a matter of considerable concern to me when we initially proposed that the Ir gene product could be the elusive T cell receptor (1).

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