In vivo priming of cytotoxic T lymphocyte responses in relation to in vitro up‐regulation of major histocompatibility complex class I molecules by short synthetic peptides

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Abstract
Cytotoxic T lymphocytes (CTL) recognize target antigens as short peptides presented by major histocompatibility complex class I molecules (MHC‐I). Externally added peptides can sensitize target cells by binding directly to MHC‐I without any need for internal processing. Those which are similar in length to endogenously processed peptides are more potent in this respect than slightly longer peptides. Peptide MHC‐I interactions can also be reflected as upregulation of MHC‐I in vitro on certain cells. We have compared the capacity of Db, Kb‐ and Ld‐binding peptides, which are slightly different in length, to up‐regulate MHC‐I in vitro with their immunogenicity in vivo, in relation to generation of CTL responses. A clear correlation between these two different functions was found. We have also modified a 9‐mer Db‐binding peptide by adding cystein to the amino terminus and lysine to the amino‐ or carboxy terminus and studied the effects on MHC‐I up‐regulation and in vivo immunogenicity. Cystein and lysine contain reactive groups which are likely to influence the binding of modified peptides into the antigen‐binding groove of Db. These small modifications of the optimal 9‐mer peptide strongly influenced their functions but still there was a correlation between MHC‐I up‐regulation and CTL responses. Up‐regulation of MHC‐I in vitro may reflect a capacity of peptides to accumulate on the surface of particular antigen‐presenting cells in vivo.