التفاصيل البيبلوغرافية
| العنوان: |
Positive selection of low responsive, potentially autoreactive T cells induced by high avidity, non-deleting interactions. |
| المؤلفون: |
Chidgey, AP, Boyd, RL |
| المصدر: |
International Immunology; Jul1998, Vol. 10 Issue 7, p999-1008, 10p |
| مستخلص: |
Using a novel cell suspension model we investigated the relative abilities of nominal peptide and variants thereof to modulate de novo positive selection of lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic T cells. Confirming our earlier findings intermediate concentrations (10-7 to 10-5 M) of the nominal agonist peptide, p33, induced CD8 co-receptor down-modulation at the level of the entire receptor and the CD8β chain as a consequence of high but non-deleting signal interactions. Agonist peptide variants caused down-modulation of the CD8β chain but to a lesser degree. An antagonist peptide capable of inducing positive selection did not cause such modifications of the co-receptor. The positively selected TCRhiCD8αα and TCRhiCD8- cells were functional but not as efficient as TCRhiCD8αβ cells, presumably due to lower avidity interactions in the absence of the CD8β chain or entire co-receptor. CD8β mRNA was absent in these cells and was not up-regulated when further stimulated with fresh antigen-presenting cells pulsed with 10-5 M p33. Effectively our data suggest that it is not the agonist or antagonist nature of a peptide per se but the overall strength of signaling that determines whether a cell will be positively or negatively selected, or die by neglect. Furthermore the agonist/antagonist properties of peptides defined at the level of mature T cell function do not unequivocally predict their effect on positive/negative selection. The ability of the T cell to down-modulate its CD8 co-receptor in response to high but non-deleting peptide interactions during positive selection allows the survival of T cells with a broader range of affinities and represents a possible mechanism by which low responsive but potentially autoreactive cells may escape into the periphery. [ABSTRACT FROM PUBLISHER] |
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| قاعدة البيانات: |
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