SINGLE-RESIDUE CHANGES IN CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES STIMULATE RESPONSES TO SELF PEPTIDES

Single-residue changes were introduced into the murine major histocomp atibility complex class I molecule H-2K(b) at positions 65 and 69, whi ch are predicted to point up from the alpha-helix of the alpha(1) doma in and not into the peptide binding groove. Mutated and wild-type gene s were transfected into the murine cell line P815 (H-2d). We present e vidence that the changes did not affect the binding of three foreign p eptides that are recognized by cytotoxic T lymphocytes (CTL) in associ ation with H-2K(b). Additionally, the mutants provoked strong alloreac tive responses in T cells from mice expressing unmutated H-2K(b). The alloreactive CTL were specific for self peptides, which could be extra cted from wild-type H-2K(b) molecules, recognized in the context of th e mutant class I.