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Low‐avidity recognition by CD4 + T cells directed to self‐antigens
Author(s) -
Gebe John A.,
Falk Ben A.,
Rock Kellee A.,
Kochik Sharon A.,
Heninger Anne K.,
Reijonen Helena,
Kwok William W.,
Nepom Gerald T.
Publication year - 2003
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200323871
Subject(s) - avidity , epitope , biology , antigen , t cell , cytotoxic t cell , major histocompatibility complex , cd8 , microbiology and biotechnology , mhc restriction , immune system , antigen presenting cell , autoimmunity , immunology , mhc class i , biochemistry , in vitro
Abstract Self‐reactive T cells populate the peripheral immune system, and likely form the reservoir from which autoreactive cells are derived. We analyzed a panel of self and non‐self peptides presented by HLA‐DR4, a class II molecule associated with autoimmunity, by immunization of mice transgenic for HLA‐DR4. Significant structural avidity for T cell recognition, as measured by MHC class II tetramer binding to CD4 + T cells was only observed in mice immunized with the non‐self antigens. T cell hybridomas were generated from mice immunized with the naturally processed self‐peptide hGAD65 (552–572) and also from mice immunized with an influenza‐derived non‐self epitope (HA 306–318). T cells specific for the self peptide failed to bind tetramers and exhibited low functional avidity as measured by the peptide concentration required to reach half‐maximum proliferation values. In contrast, T cells specific for the non‐self HA (306–318) peptide exhibited high structural and functional avidity profiles. As recently described in studies of murine CD8 + T cell function, the predominance of low avidity recognition of self‐peptide epitopes may be a characteristic feature of CD4 + T cells responding to autoantigens.