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Critical Requirement for Aspartic Acid at Position 82 of Myelin Basic Protein 73–86 for Recruitment of Vß8.2⁺ T Cells and Encephalitogenicity in the Lewis Rat

Ronald B. Smeltz^*, Marca H. M. Wauben, Norbert A. Wolf^* and Robert H. Swanborg^*

^* Departments of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201; and Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

We synthesized single amino acid-substituted peptide analogues of guinea pig myelin basic protein (MBP) 73–86 to study the importance of aspartic acid at residue 82 (QKSQRSQDENPV), which previous reports have suggested is a critical TCR contact residue. Whereas the wild-type 73–86 peptide elicited severe experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, none of the peptide analogues with substitutions at position 82 were capable of inducing EAE. The inability to cause EAE was not due to a failure to bind MHC or to elicit T cell proliferation and cytokine secretion. T cells specific for MBP73–86 did not cross-react with any of the analogues tested, further indicating the importance of this residue in T cell responses to 73–86. Analysis by flow cytometry showed that only the wild-type 73–86 peptide was capable of recruiting Vß8.2⁺ T cells, which have been shown previously to be important for disease induction. Reduced expression of the Vß8.2 TCR was also seen in Lewis rats protected from EAE by coimmunization of MBP73–86 with 73–86(82DA), despite an increase in cytokine production when both peptides were present during in vitro culture. The data indicate that aspartic acid 82 is a critical TCR contact residue and is required for the recruitment of Vß8.2⁺ T cells and the encephalitogenic activity of MBP73–86.

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