Low‐avidity recognition by CD4+ T cells directed to self‐antigens

JA Gebe, BA Falk, KA Rock, SA Kochik… - European journal of …, 2003 - Wiley Online Library
JA Gebe, BA Falk, KA Rock, SA Kochik, AK Heninger, H Reijonen, WW Kwok, GT Nepom
European journal of immunology, 2003Wiley Online Library
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 …
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.
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