Low-avidity recognition by CD4(+) T cells directed to self-antigens

University of Washington Seattle, Seattle, Washington, United States
European Journal of Immunology (Impact Factor: 4.03). 06/2003; 33(5):1409-17. DOI: 10.1002/eji.200323871
Source: PubMed


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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    • "A further analysis suggested that the weaker proliferative responses of Can f 1 and TL peptide-specific TCLs are attributed to the low frequency of TCLs with high functional TCR avidity (Fig. 2B). These results are in line with reports from other investigators, as they indicate that T cells specific to self antigens exhibit low TCR avidity whereas those specific to microbial antigens exhibit higher TCR avidity [60]–[62]. "
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    PLoS ONE 05/2014; 9(5):e98461. DOI:10.1371/journal.pone.0098461 · 3.23 Impact Factor
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    • "The absence of a bias toward nonself sequences and toward sequences with likely low HLA-A2 binding affinity (i.e., low SYFPEITHI scores) among the peptides triggering strong responses in HLA-A2 transgenic mice suggests that this immunization strategy may be readily able to overcome self-tolerance. However, it is possible that the responding T cells displayed low T-cell receptor avidity as frequently observed at least for autoreactive CD4+ T cells (30). "
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