Major role of antigen-presenting cells in the response of rat encephalitogenic T cells to myelin basic proteins.
The encephalitogenic potential of a segment of myelin basic protein in experimental autoimmune encephalomyelitis is not always mirrored by the ability of the peptide to mediate in vitro activation of encephalitogenic T cells. Recent studies from our laboratory have demonstrated that the responsiveness of Ag-specific T cells in experimental autoimmune encephalomyelitis is determined not exclusively by Ag but also by the nature of the APC. By varying APC during the in vitro selection of T cells, we could generate distinct sets of rat encephalitogenic T cells, as evidenced by the diversity of TCR usage. Here we establish the importance of APC in the activation of rat encephalitogenic T cells by myelin basic protein peptides. Peptides 69-84-Gly and (P80)68-86, which lacked stimulatory activity toward many encephalitogenic T cells in our proliferation assay when standard APC were used, become strongly stimulatory in the presence of less commonly used APC, i.e., an Ia+ T cell clone (LOA) or an Ia-inducible rat glial cell clone (F10). Nonstimulatory APC failed to activate encephalitogenic T cells even when major cytokines were added, suggesting that these cytokines are not among the factors limiting the activating potential of the APC. Thus, whether or not an immunocompetent T cell can be activated by a given Ag in an autoimmune response may be determined by the properties of APC. This finding has implications for current research efforts to identify pathogenic self proteins.
Sun
D
D
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38101.
Le
J
J
Yang
S
S
Malotkey
M
M
Coleclough
C
C
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007116:Immunization, Passive; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides