Specificity of peptide presentation by a set of hybrid mouse class I MHC molecules

Abstract

The class I molecules of the major histocompatibility complex (H–2 in mouse, HLA in man) are membrane proteins composed of a polymorphic heavy chain associated with β-2-mieroglobulin. Recent studies suggest that class I molecules present peptides derived from processed antigens to the receptor of cytolytic T cells^1,2. In particular, in the H–2^d haplotype, synthetic HLA peptides can be recognized on K^d-bearing target cells by K^d-restricted cytolytic T cells specific for HLA (ref.2). Here we analyse the specificity of presentation of two HLA peptides by a set of chimaeric K^d/D^d molecules³ to four different cytolytic T-cell clones. We identify two distinct regions within the second external (αa2) domain of K^d that contribute to its specificity as a restriction element. Our results indicate that the binding of an immunogenic peptide by a class I molecule is not always sufficient for its recognition by the T-cell antigen receptor. This suggests that the major histocompatibility complex restriction element either interacts with the T-cell antigen receptor or induces the recognized conformation of the peptide.