Specificity of peptide presentation by a set of hybrid mouse class I MHC molecules.
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 beta-2-microglobulin. Recent studies suggest that class I molecules present peptides derived from processed antigens to the receptor of cytolytic T cells. In particular, in the H-2d haplotype, synthetic HLA peptides can be recognized on Kd-bearing target cells by Kd-restricted cytolytic T cells specific for HLA. Here we analyse the specificity of presentation of two HLA peptides by a set of chimaeric Kd/Dd molecules to four different cytolytic T-cell clones. We identify two distinct regions within the second external (alpha 2) domain of Kd 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.
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D004252:DNA Mutational Analysis; D004274:DNA, Recombinant; D006183:H-2 Antigens / Q000502:physiology*; D006680:HLA Antigens / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000502:physiology*; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D004274:DNA, Recombinant; D006183:H-2 Antigens; D006680:HLA Antigens; D011971:Receptors, Immunologic