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Tetanus toxin L chain is processed by major histocompatibility complex class I and class II pathways and recognized by CD8 + or CD4 + T lymphocytes
Author(s) -
Kerblat I.,
TongianiDahshan S.,
AudeGarcia C.,
Villiers M.B.,
Drouet C.,
Marche P. N.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00032.x
Subject(s) - biology , brefeldin a , antigen processing , t cell , cd8 , microbiology and biotechnology , antigen presentation , cytotoxic t cell , antigen , biochemistry , golgi apparatus , cell , immunology , in vitro , immune system
Tetanus toxin (TeNT) is a heterodimeric protein antigen, whose light chain (L) is translocated in the cytosol of neuronal target cells specifically to cleave its substrates, vesicle-associated membrane protein-2 (VAMP-2, or synaptobrevin) or cellubrevin. We report that the L chain behaves as a nominal antigen recognized by specific T-cell clones upon either class I- or II-restricted presentation. Three types of responses are observed: (i) a TeNT- and L-specific CD8+ T-cell response, that can be inhibited in a dose-dependent manner by the proteasome inhibitor clasto-Lactacystin beta-lactone; (ii) a CD4+ T-cell response specific for L but not TeNT, with recognition of a determinant processed in a chloroquine-sensitive and brefeldin A-resistant compartment; (iii) a CD4+ T-cell response against both L and TeNT, with processing in a brefeldin A-sensitive compartment. The L chain processing was investigated in U937 cells by internalization and localization of L chain by separation of the cell content by differential centrifugation experiments. After incubation with TeNT or L chain in the presence of H chain, the L chain was predominantly distributed in the cytosolic fraction, whereas incubation with L alone led to localization in a lysosome/membrane fraction. The distribution of the TeNT L chain in both cytosolic and endocytic compartments of the antigen-presenting cell accounted for its processing by both class I and class II pathways. Furthermore, an epitope overlapping with the zinc-binding region was recognized by CD4+ and CD8+ T cells.