MULTIPLE SELF EPITOPES ON THE RHESUS POLYPEPTIDES STIMULATE IMMUNOLOGICALLY IGNORANT HUMAN T-CELLS IN-VITRO

The extent of autoreactive T cell repertoire in the normal individual has previously been unclear. Here we demonstrate that T cells from hea lthy humans can be stimulated by multiple epitopes on a self protein t o give primary proliferative responses in vitro. Synthetic 15-mer pept ides, corresponding to the sequence of a human red blood cell Rhesus p olypeptide,were tested for the ability to stimulate normal T cells. Mu ltiple peptides were found to provoke responses reproducibly, and the proliferation could be blocked consistently by antibodies to HLA-DR, b ut not -DP or -DQ. T cells from each donor proliferated in response to different patterns of peptides, but this variation in pattern was les s marked in individuals with the same HLA-DR type. The responses were comparable in kinetics to those elicited by the non-recall foreign ant igen keyhole limpet hemocyanin, and the responding cells are most comm only derived from the CD45RA(+) subpopulation, indicating that they ha d not been activated in vivo. It is considered that T cells are ''immu nologically ignorant'' of many self peptides, presumably because they correspond to cryptic epitopes that are not normally presented in vivo .