Major histocompatibility complex binding and T cell recognition of a viral nonapeptide containing a minimal tetrapeptide

Abstract

Abstract The primary immune response of cytotoxic T lymphocytes in H‐2 d and H‐2 q mice to infection with lymphocytic choriomeningitis virus is directed mostly towards the common major T cell epitope of amino acids 112–132 on the viral nucleoprotein (NP). The molecules responsible for presentation of the T cell epitope NP112‐132 are in both haplotypes the MHC class I L antigens (L d , L q ). Truncations of the amino and carboxy termini of the NP 112–132 sequence revealed the nonapeptide RPQASGVYM (NP118‐126) as a most effective peptide antigen, but even the tetrapeptide GVYM was recognized by CTL of both haplotypes in a class I antigen‐restricted specificity. When tyrosine (Y) or methionine (M) were substituted with alanine, CTL recognition of the altered nonamer required 10 6 to 10 8 times higher peptide concentrations and in one case (Y → A on L d ) the peptide was not recognized at all. Up‐modulation of the expression of L d and L q class I antigens as measured by flow cytometry correlated with the ability to present the peptide antigens. The only exception was peptide NP118‐126 (M → A), which was recognized by T cells on L‐L d and L‐L q target cells but failed to up‐regulate L d and L q antigens.