MHC class II restricted self-recognition after allostimulation: clonal analysis.

After allostimulation in vitro using a combination of HLA-A, B, C, DR, DQ, D identical but HLA-DP different homozygous typing cells, 34 T cell clones were derived. Thirty-one of them were alloreactive clones, but three clones were found to be autoreactive. One of these autoreactive clones was further expanded. In order to characterize in more detail the determinant restricting the autologous response, a panel of HLA-typed peripheral blood mononuclear cells (PBMC) or Epstein-Barr virus lymphoblastoid cell lines (EVB-LCL) was typed. A good correlation of typing responses with the self haplotype HLA-A1, B8, Cw7, DR3, DRw52, DQw2 was found. Typing responses also segregated together with this haplotype in informative families. Blocking studies using MHC class I and II specific monoclonal antibodies (MoAb) linked the restricting determinant to MHC class II molecules. The clone which was both autoproliferative and autocytotoxic bore the CD3(+), CD4(+), CD8(-), Ia(+) phenotype. Antibiotics or foreign plasma proteins were ruled out as restricted determinants.