High-Affinity Reactions Between Antigen-Specific T-Cell Receptors and Peptides Associated with Allogeneic and Syngeneic Major Histocompatibility Complex Class I Proteins

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 24; pp. 11487 - 11491
• Main Authors: Sykulev, Y, Brunmark, A, Tsomides, T J, Kageyama, S, Jackson, M, Peterson, P A, Eisen, H N
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 22.11.1994; National Acad Sciences; National Academy of Sciences
• Subjects: AIDS/HIV; Amino Acid Sequence; Animals; Antibodies; Antigen presenting cells; Biochemistry; CD8-Positive T-Lymphocytes - immunology; Cellular biology; Histocompatibility Antigens Class I - immunology; Immunity (Disease); Ketoglutarate Dehydrogenase Complex - chemistry; Ketoglutarate Dehydrogenase Complex - immunology; Kinetics; Ligands; Major histocompatibility complex genes; Mathematical constants; Mice; Molecular Sequence Data; Molecules; Ovalbumin - chemistry; Ovalbumin - immunology; Peptides - chemistry; Peptides - immunology; Protein Binding; Receptors, Antigen, T-Cell - metabolism; T cell antigen receptors; T lymphocytes; Transplantation immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.24.11487

We report here that the intrinsic affinities of the antigen-specific T-cell receptors (TCR) of two unrelated CD8+T-cell clones for their respective peptide-major histocompatibility complex (MHC) ligands are higher than the values generally thought to prevail for TCR. The TCR of one clone (2C) binds an allogeneic class I MHC protein (Ld) in association with an α-ketoglutarate dehydrogenase nonapeptide (QLSPFPFDL, termed QL9) with an intrinsic affinity (intrinsic equilibrium association constant) of 1-2 x 107M-1. The TCR of the other clone (4G3) binds a syngeneic class I MHC protein (Kb) in association with an ovalbumin octapeptide (SIINFEKL, termed pOV8) with an intrinsic affinity of 1.5 x 106M-1. A comparison of the two clones, combined with current views of T-cell repertoire selection in the thymus, leads us to propose that TCR affinities are generally likely to be higher for allogeneic MHC-peptide complexes than for syngeneic MHC-peptide complexes.