Induction of a heterogeneous TCR repertoire in (PL/JXSJL/J)F1 mice by myelin basic protein peptide Ac1-11 and its analog Ac1-11[4A]
| Autor: | Dawn E. Smilek, Jayne S. Danska, C.I. Pearson, Hugh O. McDevitt |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Proteolipid protein 1 T cell Molecular Sequence Data Immunology Dose-Response Relationship Immunologic Receptors Antigen T-Cell Mice Inbred Strains Biology Major histocompatibility complex Mice medicine Animals Amino Acid Sequence Molecular Biology Clonal Anergy Binding Sites Hybridomas Peptide analog Base Sequence Experimental autoimmune encephalomyelitis T-cell receptor Myelin Basic Protein medicine.disease Molecular biology Peptide Fragments Myelin basic protein medicine.anatomical_structure biology.protein Alpha chain |
| Zdroj: | Molecular Immunology. 34:781-792 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/s0161-5890(97)00058-8 |
| Popis: | Experimental autoimmune encephalomyelitis (EAE) serves as a rodent model of the autoimmune disease multiple sclerosis. In mice, EAE is induced by immunizing with spinal cord homogenate, components of the myelin sheath, such as myelin basic protein (MBP) or proteolipid protein (PLP), or peptides derived from these components. EAE can be induced in H-2u or (H-2u x H-2s)F1 mice with the N-terminal peptide of MBP, Ac1-11. Coimmunization with Ac1-11 and Ac1-11[4A], an analog in which lysine at position four is substituted with alanine, prevents EAE. The mechanism of inhibition has not been elucidated, but probably does not work through MHC blockade, T cell anergy or clonal elimination of encephalitogenic T cells. We have isolated T cell clones and hybridomas from (PL/J x SJL/J)F1 mice immunized with either Ac1-11 alone or Ac1-11 and Ac1-11[4A] and analysed these cells for differences in their T cell receptor repertoire and in vitro response. Although T cells elicited by coinjection of Ac1-11 and Ac1-11[4A] expressed TCR that used V alpha and Vbeta gene elements similar to those elicited by Ac1-11 alone, they differed in the sequences of the junctional region of the alpha chain. Most of these T cells also responded less well to Ac1-11 in vitro, suggesting that coinjection of Ac1-11 and Ac1-11[4A] preferentially activates T cells bearing TCR of different affinity for Ac1-11 bound to I-A(u), and which may therefore be less encephalitogenic. Furthermore, our results show that a more diverse repertoire of V alpha and Vbeta genes are elicited by Ac1-11 in (PL/J x SJL/J)F1 mice compared to PL/J and B10.PL mice, providing further evidence that a restricted TCR repertoire is not required for the development of autoimmune disease. |
| Databáze: | OpenAIRE |
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