Presentation of autoantigen by human T cells.
Activated human T cells express MHC class II and have been shown to present foreign Ag to autologous T cells. We now demonstrate that MHC class II+ T cell clones can present myelin basic protein (MBP) peptide autoantigen in the absence of traditional APC to autologous MBP reactive T cell clones. MBP peptide-pulsed T cell clones specifically stimulated autologous MBP-reactive T cell clones to flux calcium and proliferate. Activation responses were peptide epitope specific and blocked by mAb to MHC class II, indicating a TCR-mediated response. In addition, mAb to the adhesion molecules LFA-3, CD2, LFA-1, CD29, and to the tyrosine phosphatase CD45 also inhibited proliferation, indicating the involvement of T to T cell interactions. In contrast to peptide Ag, T cell clones did not respond to autologous T cells pulsed with HPLC-purified MBP, suggesting that T cells are unable to process whole MBP. However, batch-purified MBP Ag preparations containing lower m.w. breakdown products were presented by T cells, indicating that naturally occurring breakdown products of autoantigens could be presented by activated T cells in vivo. These results raise the possibility that T cell presentation of autoantigen at inflammatory sites may be important in regulation of immune responses to self Ag.
LaSalle
J M
JM
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Ota
K
K
Hafler
D A
DA
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology; D001324:Autoantigens / Q000096:biosynthesis*; D018801:CD2 Antigens; D018968:CD58 Antigens; D000939:Epitopes; D006681:HLA-D Antigens / Q000276:immunology; D006649:Histocompatibility Antigens / Q000502:physiology; D006801:Humans; D019012:Integrin beta1; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D011971:Receptors, Immunologic / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D001324:Autoantigens; D018801:CD2 Antigens; D018968:CD58 Antigens; D000939:Epitopes; D006681:HLA-D Antigens; D006649:Histocompatibility Antigens; D019012:Integrin beta1; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D011971:Receptors, Immunologic; D017493:Leukocyte Common Antigens