Relative contribution of 'determinant selection' and 'holes in the T-cell repertoire' to T-cell responses

Academic Article

Abstract

  • Using BALB/c and CBA/J mice, the I-region associated (Ia) binding capacity and T-cell immunogenicity of a panel of 14 overlapping peptides that span the entire sequence of the protein staphylococcal nuclease (Nase) was examined to evaluate major histocompatibility gene complex (MHC) control of T-cell responses. Ia binding and Ia-restricted T-cell immunogenicity could be determined for a total of 54 peptide-MHC combinations. Only 30% of the 54 instances examined involved detectable Ia binding, but they represented almost all (12 of 13) of the immune responses found. However, binding to Ia was not sufficient to ensure T-cell immunogenicity, since only 70% of the binding events were productive - i.e., were associated with an immune response. Thus, Ia molecules have the expected characteristics of a highly permissive capacity for antigen interaction that allows them to function as restriction elements for a large universe of antigens. On the other hand, since the Ia molecules cannot distinguish between self and non-self, not all antigen-Ia interactions would be permitted to elicit a T-cell response. It appears that both Ia binding ('determinant selection') and T-cell repertoire act in concert to define the immune response status of an individual toward any particular T-cell epitope.
  • Authors

    Digital Object Identifier (doi)

    Pubmed Id

  • 1388445
  • Author List

  • Schaeffer EB; Sette A; Johnson DL; Bekoff MC; Smith JA; Grey HM; Buus S
  • Start Page

  • 4649
  • End Page

  • 4653
  • Volume

  • 86
  • Issue

  • 12