Peptide recognition by T-cell clones of an HLA-DRB1*1501/*0901 heterozygous donor is promiscuous only between parental alleles.

The HLA class II isotype and allelic restrictions of peptide recognition were analyzed with T cells from a DRB1*1501/DRB1*0901 heterozygous donor. Nineteen T cell clones, all directed against the single mycobacterial epitope p21-40 were tested with HLA homozygous lymphoblastoid cell lines as antigen-presenting cells. The most striking finding has been, that several DR isotype restricted clones recognized the peptide in the context of both parental, but not of unrelated alleles. In contrast, DQ and DP restricted clones responded in the context of one parental allele only. Most DR promiscuous clones produced interferon-gamma but not IL-4, whereas most DQ and DP clones produced IL-4. We postulate that the confinement of DR promiscuity only to the parental alleles was established possibly during thymic maturation of T cells and that the proportions between monogamous and promiscuous T cells may play a role in the MHC mediated influences on host resistance to infections and other immune responses.