期刊
JOURNAL OF IMMUNOLOGY
卷 193, 期 7, 页码 3267-3277出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1400523
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资金
- INSERM
- Centre National de la Recherche Scientifique
- Association pour la Recherche sur la Sclerose in Plaques
- Medical Research Foundation [DEQ20090515409]
- Italian Federation for Multiple Sclerosis [2012/B/6]
The recognition of multiple ligands by a single TCR is an intrinsic feature of T cell biology, with important consequences for physiological and pathological processes. Polyspecific T cells targeting distinct self-antigens have been identified in healthy individuals as well as in the context of autoimmunity. We have previously shown that the 2D2 TCR recognizes the myelin oligodendrocyte glycoprotein epitope (MOG)(35-55) as well as an epitope within the axonal protein neurofilament medium (NF-M15-35) in H-2(h) mice. In this study, we assess whether this cross-reactivity is a common feature of the MOG(35-55)-specific T cell response. To this end, we analyzed the CD4 T cell response of MOG(35-55)-immunized C57BL/6 mice for cross-reactivity with NF-M15-35. Using Ag recall responses, we established that an important proportion of MOG(35-55)-specific CD4 T cells also responded to NF-M15-35 in all mice tested. To study the clonality of this response, we analyzed 22 MOG(35-55)-specific T cell hybridomas expressing distinct TCR. Seven hybridomas were found to cross-react with NF-M15-35. Using an alanine scan of NF-M18-30 and an in silico predictive model, we dissected the molecular basis of cross-reactivity between MOG(35-55) and NF-M15-35. We established that NF-M F24, R26, and V27 proved important TCR contacts. Strikingly, the identified TCR contacts are conserved within MOG(38-50). Our data indicate that due to linear sequence homology, part of the MOG(35-55)-specific T cell repertoire of all C57BL/6 mice also recognizes NF-M15-35, with potential implications for CNS autoimmunity.
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