An autologous self-antigen differentially regulates expression of I-A glycoproteins and B7 costimulatory molecules on CD4- CD8- T helper cells.
During inflammation, T helper cells transiently express class II major histocompatibility complex (MHC) glycoproteins and present antigens to other T cells. To assess involvement of self-antigens in the generation of T cell antigen-presenting cell (T-APC) activity, rat (R) myelin basic protein (MBP) was used to stimulate a rat CD4-CD8- T cell clone. RMBP induced T cell surface expression of class II MHC glycoproteins and T-APC activity, although RMBP did not elicit interleukin (IL-2) production or proliferation. When added to culture with the strong agonist guinea pig (GP) MBP, RMBP acted as a partial antagonist and inhibited responses of IL-2 production, proliferation, and T cell expression of B7.1. RMBP did not, however, efficiently antagonize GPMBP-induced I-A expression on T cells. These findings indicate that the self-antigen RMBP specifically induces accumulation of I-A/peptide complexes at signaling thresholds that inhibit pathogenic autoimmune responses. Overall, this study suggests a role for self-antigens in the generation of B7-deficient T-APC activity as a mechanism of tolerance in experimental autoimmune encephalomyelitis.
Walker
M R
MR
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, USA.
White
G A
GA
Nardella
J P
JP
Mannie
M D
MD
D016475:3T3 Cells; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; D006023:Glycoproteins / Q000096:biosynthesis*; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000037:antagonists & inhibitors; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism*
D015703:Antigens, CD; D001324:Autoantigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; C497965:Cd86 protein, mouse; C497966:Cd86 protein, rat; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell