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 healthy humans can be stimulated by multiple epitopes on a self protein to give primary proliferative responses in vitro. Synthetic 15-mer peptides, corresponding to the sequence of a human red blood cell Rhesus polypeptide, were tested for the ability to stimulate normal T cells. Multiple peptides were found to provoke responses reproducibly, and the proliferation could be blocked consistently by antibodies to HLA-DR, but not -DP or -DQ. T cells from each donor proliferated in response to different patterns of peptides, but this variation in pattern was less marked in individuals with the same HLA-DR type. The responses were comparable in kinetics to those elicited by the non-recall foreign antigen keyhole limpet hemocyanin, and the responding cells are most commonly derived from the CD45RA+ subpopulation, indicating that they had not been activated in vivo. It is considered that T cells are "immunologically ignorant" of many self peptides, presumably because they correspond to cryptic epitopes that are not normally presented in vivo.
Barker
R N
RN
Department of Pathology and Microbiology, University of Bristol, GB.
Elson
C J
CJ
D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D012204:Rh-Hr Blood-Group System / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000939:Epitopes; D006681:HLA-D Antigens; D007519:Isoantigens; D012204:Rh-Hr Blood-Group System; D006433:Hemocyanins; D017493:Leukocyte Common Antigens; C032808:keyhole-limpet hemocyanin