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Myelin basic protein peptide specificity and T‐cell receptor gene usage of HPRT mutant T‐cell clones in patients with multiple sclerosis
Author(s) -
Lodge Patricia A.,
Allegretta Mark,
Steinman Lawrence,
Sriram Subramaniam
Publication year - 1994
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410360508
Subject(s) - myelin basic protein , biology , microbiology and biotechnology , myelin , hypoxanthine guanine phosphoribosyltransferase , mutant , t cell , gene , biochemistry , immunology , immune system , endocrinology , central nervous system
Characterization of T cells responding to autoantigens is central to understanding autoimmune disease. We have used somatic mutation at the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene as an index of T‐cell amplification in vivo. With this strategy we previously showed that myelin basic protein–reactive T cells can be isolated only from the HPRT mutant T‐cell population cultured from the peripheral blood of multiple sclerosis patients and not from normal individuals. In this study, 165 HPRT mutant and 104 wild‐type clones were examined for their reactivity to myelin basic protein and overlapping peptides of myelin basic protein. Five HPRT mutant clones that recognized myelin basic protein and myelin basic protein peptides along with three clones that responded to myelin basic protein peptide alone were isolated. All but one of the eight clones recognized peptides derived from the carboxy terminus of myelin basic protein (p84‐168). Sequence analysis showed heterogeneous expression of T‐cell receptor Vα and Vβ genes and CDR3s. These studies showed that in vivo amplified autoimmune T cells from patients with long‐standing disease use diverse T‐cell receptor elements in the recognition of C‐terminal myelin basic protein peptides.