SPECIFICITY AND DEGENERACY OF MINOR HISTOCOMPATIBILITY ANTIGEN-SPECIFIC MHC-RESTRICTED CTL

Random peptide libraries were employed to investigate the specificity of Ag recognition by H-3-specific, H-2K(b)-restricted CTL clones. The peptide libraries consist of octapeptides with one defined sequence po sition and mixtures of 19 amino acids (all proteinogenic amino acids e xcept for cysteine) in the remaining seven sequence positions. The com plete set of 152 peptide libraries includes all octapeptides possible with these amino acids. Responses of the CTL clones to these peptide l ibraries reveal patterns of preferred epitope amino acids. Depending o n the CTL clone tested, varying numbers of different amino acids were identified for the different sequence positions indicating degeneracy of Ag recognition. Sequences for synthetic epitopes active at low pM c oncentrations could be deduced from these patterns. They confirm that TCRs of CTL clones do not exhibit specificity for unique ligand struct ures but rather can interact with sets of ligands. The sequences of pe ptides recognized by a single clone exhibit great sequence heterogenei ty.