Antigen-specific suppression of human antibody responses by allogeneic T cells. III. Role of the major histocompatibility complex.
Specific antibody responses obtained in vitro from human blood mononuclear cells (PBM) were profoundly suppressed by allogeneic T cells. Experiments carried out with combinations of cells from HLA identical siblings, and HLA identical but unrelated donors, showed that suppression depended upon HLA incompatibility between responding PBM and allogeneic Ts. In order to map the specific HLA loci concerned, a series of experiments were undertaken using combinations of cells from a large number of HLA typed donors. Significant suppression was found to occur in every combination of HLA incompatible cells tested, including those with nonidentity at HLA-A, B, DR, A and DR, or B and DR, suggesting that suppression can be generated by nonidentity at class I or class II loci. With some HLA-A homozygous donors, however, a dominant role for class I (HLA-A) antigens was indicated by the finding of one-directional suppression in combinations where the HLA-A locus was seen as foreign by one partner only (A3,----A2,3; and A2----A2,26). Similar one-directional suppression was also seen with cells from a pair of siblings who were HLA identical except for a single A locus antigen arising from an HLA-A/B recombination (A3,----A3,1). These results indicate an important, but not exclusive role for class I MHC antigens in the activation of allogeneic Ts. The way in which this occurs is unknown, but one possibility is that it results from the activation of normal antigen-specific Ts by the interaction of their receptors for self-MHC with cross-reacting alloantigens.
D000483:Alleles; D000917:Antibody Formation; D002478:Cells, Cultured; D008040:Genetic Linkage; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D006680:HLA Antigens