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J Immunol. 2014 Oct 1;193(7):3267-77. doi: 10.4049/jimmunol.1400523. Epub 2014 Aug 18.

Bispecificity for myelin and neuronal self-antigens is a common feature of CD4 T cells in C57BL/6 mice.

Author information

1
INSERM, U1043, Toulouse F-31300, France; Centre National de la Recherche Scientifique, U5282, Toulouse F-31300, France; Centre de Physiopathologie Toulouse-Purpan, Université Toulouse 3, Toulouse F-31300, France;
2
Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Chemical Support, Weizmann Institute of Science, Rehovot 7610001, Israel;
3
La Jolla Institute for Allergy and Immunology, San Diego, CA 92109;
4
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
5
INSERM, U1043, Toulouse F-31300, France; Centre National de la Recherche Scientifique, U5282, Toulouse F-31300, France; Centre de Physiopathologie Toulouse-Purpan, Université Toulouse 3, Toulouse F-31300, France; Département d'Immunologie, Centre Hospitalier Universitaire Toulouse, Hôpital Purpan, Toulouse F-31300, France roland.liblau@inserm.fr.

Abstract

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(b) mice. In this study, we assess whether this cross-reactivity is a common feature of the MOG35-55-specific T cell response. To this end, we analyzed the CD4 T cell response of MOG35-55-immunized C57BL/6 mice for cross-reactivity with NF-M15-35. Using Ag recall responses, we established that an important proportion of MOG35-55-specific CD4 T cells also responded to NF-M15-35 in all mice tested. To study the clonality of this response, we analyzed 22 MOG35-55-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 MOG35-55 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 MOG38-50. Our data indicate that due to linear sequence homology, part of the MOG35-55-specific T cell repertoire of all C57BL/6 mice also recognizes NF-M15-35, with potential implications for CNS autoimmunity.

PMID:
25135834
DOI:
10.4049/jimmunol.1400523
[Indexed for MEDLINE]
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