Clonotypic heterogeneity of Lewis rat T cells specific for the encephalitogenic 68-86 region of myelin basic protein.
Experimental autoimmune encephalomyelitis was induced in a Lewis rat by sensitization with synthetic peptide GP68-86, representing the 68-86 sequence of guinea pig myelin basic protein (GPMBP). To delineate T cell determinants of GP68-86, lymph node cells from this rat were activated in culture with GP68-86 and were fused with cells of the mouse thymoma BW5147. The resultant hybrids were cloned by limiting dilution and screened for GP68-86-evoked secretion of IL2 in the presence of rat splenocytes. Twelve T cell hybrids derived in this manner were tested for reactivity to different heterologous species of MBP as well as to substituted or truncated analogs of GP68-86. The hybrids generally exhibited potent reactivity to GPMBP but differed markedly in their reactivity to autologous rat MBP (RMBP). A few exceptional hybrids exhibited crossreactivity with peptides in which native serine75 or serine80 residues of GPMBP were substituted with either alanine75 (A75) or proline80 (P80) residues. These cross-reactive hybrids also possessed high levels of anti-RMBP reactivity. The remaining hybrids were unresponsive to the A75 and P80 substituted peptides and, with one exception, had relatively low levels of anti-RMBP reactivity. Unique reactivity patterns were also revealed by hybrid responses to peptides having modified C-terminal 84-86 residues. In summary, the contrasting fine specificities of different hybrids indicated that several distinct clones of T cells mediate the immune response of Lewis rats against the 68-86 region of GPMBP. Furthermore, heterogeneity in the hybrid response to "self" RMBP may reflect substantial differences in encephalitogenic potency of the T cell clones from which these hybrids were derived.
Mannie
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MD
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109.
Paterson
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PY
U'Prichard
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DC
Thomas
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DW
D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D006801:Humans; D006822:Hybrid Cells; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew / Q000276:immunology*; D011919:Rats, Inbred Strains / Q000276:immunology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D004676:Myelin Basic Protein