The clonal composition of myelin basic protein-reactive encephalitogenic T cell populations is influenced both by the structure of relevant antigens and the nature of antigen-presenting cells.
Studies of experimental autoimmune encephalomyelitis (EAE) in rodents have revealed that encephalitogenic T cell lines reactive with myelin basic protein (BP) are frequently dominated by clones expressing a restricted T cell receptor repertoire. Using the rat EAE model, we have begun to examine the basis for clonal dominance within BP-reactive T cell lines. We find that variations introduced into the standard protocol of periodic antigen stimulation produce marked shifts in the representation of different clones within encephalitogenic T cell populations. For example, altering the source of antigen-presenting cells (APC), while holding antigen (BP) constant, and substituting BP from guinea pig (GPBP) for that of the rat antigen (RBP) with constant APC, both cause shifts in the composition of the dominant clones within BP-reactive T cell lines. Our results suggest that: (i) adherence to an invariant protocol of antigen challenge may lead to an underestimation of the diversity of BP-reactive encephalitogenic T cell populations; and (ii) the minor structural differences between GPBP and RBP not only cause the weak immunogenicity of RBP but also result in the alteration of different T cell subsets. These observations indicate that apparent restrictions upon the repertoire of autoimmune T cells should be interpreted with caution when such cells are elicited by immunization with foreign antigens.
Sun
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Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38101.
Hu
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Coleclough
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D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001483:Base Sequence; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta