Requirement for Diverse, Low-Abundance Peptides in Positive Selection of T Cells

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Science  01 Jan 1999:
Vol. 283, Issue 5398, pp. 67-70
DOI: 10.1126/science.283.5398.67

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Whether a single major histocompatibility complex (MHC)–bound peptide can drive the positive selection of large numbers of T cells has been a controversial issue. A diverse population of self peptides was shown to be essential for the in vivo development of CD4 T cells. Mice in which all but 5 percent of MHC class II molecules were bound by a single peptide had wild-type numbers of CD4 T cells. However, when the diversity within this 5 percent was lost, CD4 T cell development was impaired. Blocking the major peptide–MHC complex in thymus organ culture had no effect on T cell development, indicating that positive selection occurred on the diverse peptides present at low levels. This requirement for peptide diversity indicates that the interaction between self peptides and T cell receptors during positive selection is highly specific.

  • * To whom correspondence should be addressed at Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98195, USA. E-mail: sasha{at}

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