Recognition of MHC Class I-Bound Peptides by TCR

A prerequisite for CTL-mediated immune response is the formation of the MHC-class I-peptide complex and subsequent recognition by the T-cell repertoire, which can be analyzed in cell lysis assays with MCr-loaded target cells. Chromium release is a measure for peptide-induced cell lysis by CTL, and indicates the potency of the peptide to serve as an allele-specific epitope. A synthetic epitope has been identified with the peptide library approach to elucidate the molecular basis for the observed cross-recognition of two ligands by a single receptor [53]. 

Screening of 152 0/X7 peptide libraries on cytolysis of target cells by several CTL clones showed clone-specific Recognition Patterns which allow the deduction of synthetic T-cell epitopes effective in the concentrations also typical for naturally occurring epitopes [54,55]. The degree of degeneracy is characteristic for a certain CTL clone and is also represented in the Recognition Pattern of the peptide library. 

The approach succeeded in the construction of functional mimics of tumor epitopes. One peptide was identified that induces a CTL response in vivo and thus represents the functional mimicries of a CTL epitope. The value of peptide libraries for the identifica- 

Combinatorial peptide libraries, either completely random or characterized by one or several defined positions, are useful tools for the identification of the critical features of MHC class I binding peptides and of natural and synthetic epitopes. The complete Recognition Pattern of an 0/X7 library with 152 individual peptide mixtures represents the influence of amino acid residues on mediating contact to the MHC class I molecules and of residues crucial for recognition by the TCR [54,55]. 

A major hindrance for transplantation arises from the high frequency of alloreactive T cells, although the molecular basis of alloreactivity remains elusive. Recently, a combinatorial peptide library was used to study I-Ep-alloreactivity of a hemoglobin (64-76)/ -Ek- 

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